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1. Impulse dispersion of aerosols during playing wind instruments

Author

Sophia Gantner, Matthias Echternach, Reinhard Veltrup, Caroline Westphalen, Marie Christine Köberlein, Liudmila Kuranova, Gregor Peters, Bernhard Jakubaß, Tobias Benthaus, Michael Döllinger, and Stefan Kniesburges

Subjects
Medicine, Science
Abstract

Musical activities, especially singing and playing wind instruments, have been singled out as potentially high-risk activities for the transmission of SARS CoV-2, due to a higher rate of aerosol production and emission. Playing wind instruments can produce condensation, droplets of saliva, and aerosol particles, which hover and spread in the environmental air’s convectional flows and which can be potentially infectious. The aim of this study is to investigate the primary impulse dispersion of aerosols that takes place during the playing of different wind instruments as compared to breathing and to speaking. Nine professional musicians (3 trumpeters, 3 flautists and 3 clarinetists) from the Bavarian Symphony Orchestra performed the main theme from the 4th movement of Ludwig van Beethoven‘s 9th symphony in different pitches and loudness. The inhaled air volume was marked with small aerosol particles produced using a commercial e-cigarette. The expelled aerosol cloud was recorded by cameras from different perspectives. Afterwards, the dimensions and dynamics of the aerosol cloud were measured by segmenting the video footage at every time point. Overall, the flutes produced the largest dispersion at the end of the task, reaching maximum forward distances of 1.88 m. An expulsion of aerosol was observed in different directions: upwards and downwards at the mouthpiece, at the end of the instrument, and along the flute at the key plane. In comparison, the maximum impulse dispersions generated by the trumpets and clarinets were lower in frontal and lateral direction (1.2 m and 1.0 m towards the front, respectively). Also, the expulsion to the sides was lower.

Published
2022

2. Efficient Biomedical Image Segmentation on EdgeTPUs at Point of Care

Author

Andreas M. Kist and Michael Dollinger

Subjects
EdgeTPU, convolutional neural network, coral, semantic segmentation, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract

The U-Net architecture is a state-of-the-art neural network for semantic image segmentation that is widely used in biomedical research. It is based on an encoder-decoder framework and its vanilla version shows already high performance in terms of segmentation quality. Due to its large parameter space, however, it has high computational costs on both, CPUs and GPUs. In a research setting, inference time is relevant, but not crucial for the results. However, especially in mobile, clinical applications a light and fast variant would allow deep-learning assisted, objective diagnosis at the point of care. In this work, we suggest an optimized, tiny-weight U-Net for an inexpensive hardware accelerator. We first mined the U-Net architecture to reduce computational complexity to increase runtime performance by simultaneously keeping the accuracy on a high level. Using an open, biomedical dataset for high-speed videoendoscopy (BAGLS), we show that we can dramatically reduce the parameter space and computations by over 99.8% while keeping the segmentation performance at 95% of our baseline. Using a custom upscaling routine, we further successfully deployed our optimized U-Net to an EdgeTPU hardware accelerator to gain cost-effective speed improvements on conventional computers and to showcase the applicability of EdgeTPUs for biomedical imaging processing of large images on portable devices. Combining the optimized architecture and the EdgeTPU, we gain a speedup of >79-times compared to our initial baseline while keeping high accuracy. This combination allows to provide immediate results to the clinician, especially in constrained computational environments, and an objective diagnosis at the point of care.

Published
2020
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3. Determination of Clinical Parameters Sensitive to Functional Voice Disorders Applying Boosted Decision Stumps

Author

Patrick Schlegel, Andreas M. Kist, Marion Semmler, Michael Dollinger, Melda Kunduk, Stephan Durr, and Anne Schutzenberger

Subjects
Parameters, boosted decision Stumps, classification, functional dysphonia, Computer applications to medicine. Medical informatics, R858-859.7, Medical technology, R855-855.5
Abstract

Background: Various voice assessment tools, such as questionnaires and aerodynamic voice characteristics, can be used to assess vocal function of individuals. However, not much is known about the best combinations of these parameters in identification of functional dysphonia in clinical settings. Methods: This study investigated six scores from clinically commonly used questionnaires and seven acoustic parameters. 514 females and 277 males were analyzed. The subjects were divided into three groups: one healthy group (N01) (49 females, 50 males) and two disordered groups with perceptually hoarse (FD23) (220 females, 96 males) and perceptually not hoarse (FD01) (245 females, 131 males) sounding voices. A tree stumps Adaboost approach was applied to find the subset of parameters that best separates the groups. Subsequently, it was determined if this parameter subset reflects treatment outcome for 120 female and 51 male patients by pairwise pre- and post-treatment comparisons of parameters. Results: The questionnaire “Voice-related-quality-of-Life” and three objective parameters (“maximum fundamental frequency”, “maximum Intensity” and “Jitter Percent”) were sufficient to separate the groups (accuracy ranging from 0.690 (FD01 vs. FD23, females) to 0.961 (N01 vs. FD23, females)). Our study suggests that a reduced parameter subset (4 out of 13) is sufficient to separate these three groups. All parameters reflected treatment outcome for patients with hoarse voices, Voice-related-quality-of-Life showed improvement for the not hoarse group (FD01). Conclusion: Results show that single parameters are insufficient to separate voice disorders but a set of several well-chosen parameters is. These findings will help to optimize and reduce clinical assessment time.

Published
2020
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4. 3D-FV-FE Aeroacoustic Larynx Model for Investigation of Functional Based Voice Disorders

Author

Sebastian Falk, Stefan Kniesburges, Stefan Schoder, Bernhard Jakubaß, Paul Maurerlehner, Matthias Echternach, Manfred Kaltenbacher, and Michael Döllinger

Subjects
computational fluid dynamics, computational aero acoustics, glottal insufficiency, left-right asymmetry, posterior gap, simVoice (numerical larynx model), Physiology, QP1-981
Abstract

For the clinical analysis of underlying mechanisms of voice disorders, we developed a numerical aeroacoustic larynx model, called simVoice, that mimics commonly observed functional laryngeal disorders as glottal insufficiency and vibrational left-right asymmetries. The model is a combination of the Finite Volume (FV) CFD solver Star-CCM+ and the Finite Element (FE) aeroacoustic solver CFS++. simVoice models turbulence using Large Eddy Simulations (LES) and the acoustic wave propagation with the perturbed convective wave equation (PCWE). Its geometry corresponds to a simplified larynx and a vocal tract model representing the vowel /a/. The oscillations of the vocal folds are externally driven. In total, 10 configurations with different degrees of functional-based disorders were simulated and analyzed. The energy transfer between the glottal airflow and the vocal folds decreases with an increasing glottal insufficiency and potentially reflects the higher effort during speech for patients being concerned. This loss of energy transfer may also have an essential influence on the quality of the sound signal as expressed by decreasing sound pressure level (SPL), Cepstral Peak Prominence (CPP), and Vocal Efficiency (VE). Asymmetry in the vocal fold oscillations also reduces the quality of the sound signal. However, simVoice confirmed previous clinical and experimental observations that a high level of glottal insufficiency worsens the acoustic signal quality more than oscillatory left-right asymmetry. Both symptoms in combination will further reduce the quality of the sound signal. In summary, simVoice allows for detailed analysis of the origins of disordered voice production and hence fosters the further understanding of laryngeal physiology, including occurring dependencies. A current walltime of 10 h/cycle is, with a prospective increase in computing power, auspicious for a future clinical use of simVoice.

Published
2021
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5. Interdependencies between acoustic and high-speed videoendoscopy parameters.

Author

Patrick Schlegel, Andreas M Kist, Melda Kunduk, Stephan Dürr, Michael Döllinger, and Anne Schützenberger

Subjects
Medicine, Science
Abstract

In voice research, uncovering relations between the oscillating vocal folds, being the sound source of phonation, and the resulting perceived acoustic signal are of great interest. This is especially the case in the context of voice disorders, such as functional dysphonia (FD). We investigated 250 high-speed videoendoscopy (HSV) recordings with simultaneously recorded acoustic signals (124 healthy females, 60 FD females, 44 healthy males, 22 FD males). 35 glottal area waveform (GAW) parameters and 14 acoustic parameters were calculated for each recording. Linear and non-linear relations between GAW and acoustic parameters were investigated using Pearson correlation coefficients (PCC) and distance correlation coefficients (DCC). Further, norm values for parameters obtained from 250 ms long sustained phonation data (vowel /i/) were provided. 26 PCCs in females (5.3%) and 8 in males (1.6%) were found to be statistically significant (|corr.| ≥ 0.3). Only minor differences were found between PCCs and DCCs, indicating presence of weak non-linear dependencies between parameters. Fundamental frequency was involved in the majority of all relevant PCCs between GAW and acoustic parameters (19 in females and 7 in males). The most distinct difference between correlations in females and males was found for the parameter Period Variability Index. The study shows only weak relations between investigated acoustic and GAW-parameters. This indicates that the reduction of the complex 3D glottal dynamics to the 1D-GAW may erase laryngeal dynamic characteristics that are reflected within the acoustic signal. Hence, other GAW parameters, 2D-, 3D-laryngeal dynamics and vocal tract parameters should be further investigated towards potential correlations to the acoustic signal.

Published
2021
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6. Laryngeal Pressure Estimation With a Recurrent Neural Network

Author

Pablo Gomez, Anne Schutzenberger, Marion Semmler, and Michael Dollinger

Subjects
High-speed video, inverse problem, recurrent neural networks, vocal fold dynamics, voice physiology, Computer applications to medicine. Medical informatics, R858-859.7, Medical technology, R855-855.5
Abstract

Quantifying the physical parameters of voice production is essential for understanding the process of phonation and can aid in voice research and diagnosis. As an alternative to invasive measurements, they can be estimated by formulating an inverse problem using a numerical forward model. However, high-fidelity numerical models are often computationally too expensive for this. This paper presents a novel approach to train a long short-term memory network to estimate the subglottal pressure in the larynx at massively reduced computational cost using solely synthetic training data. We train the network on synthetic data from a numerical two-mass model and validate it on experimental data from 288 high-speed ex vivo video recordings of porcine vocal folds from a previous study. The training requires significantly fewer model evaluations compared with the previous optimization approach. On the test set, we maintain a comparable performance of 21.2% versus previous 17.7% mean absolute percentage error in estimating the subglottal pressure. The evaluation of one sample requires a vanishingly small amount of computation time. The presented approach is able to maintain estimation accuracy of the subglottal pressure at significantly reduced computational cost. The methodology is likely transferable to estimate other parameters and training with other numerical models. This improvement should allow the adoption of more sophisticated, high-fidelity numerical models of the larynx. The vast speedup is a critical step to enable a future clinical application and knowledge of parameters such as the subglottal pressure will aid in diagnosis and treatment selection.

Published
2019
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7. Influence of spatial camera resolution in high-speed videoendoscopy on laryngeal parameters.

Author

Patrick Schlegel, Melda Kunduk, Michael Stingl, Marion Semmler, Michael Döllinger, Christopher Bohr, and Anne Schützenberger

Subjects
Medicine, Science
Abstract

In laryngeal high-speed videoendoscopy (HSV) the area between the vibrating vocal folds during phonation is of interest, being referred to as glottal area waveform (GAW). Varying camera resolution may influence parameters computed on the GAW and hence hinder the comparability between examinations. This study investigates the influence of spatial camera resolution on quantitative vocal fold vibratory function parameters obtained from the GAW. In total 40 HSV recordings during sustained phonation (20 healthy males and 20 healthy females) were investigated. A clinically used Photron Fastcam MC2 camera with a frame rate of 4000 fps and a spatial resolution of 512×256 pixels was applied. This initial resolution was reduced by pixel averaging to (1) a resolution of 256×128 and (2) to a resolution of 128×64 pixels, yielding three sets of recordings. The GAW was extracted and in total 50 vocal fold vibratory parameters representing different features of the GAW were computed. Statistical analyses using SPSS Statistics, version 21, was performed. 15 Parameters showing strong mathematical dependencies with other parameters were excluded from the main analysis but are given in the Supporting Information. Data analysis revealed clear influence of spatial resolution on GAW parameters. Fundamental period measures and period perturbation measures were the least affected. Amplitude perturbation measures and mechanical measures were most strongly influenced. Most glottal dynamic characteristics and symmetry measures deviated significantly. Most energy perturbation measures changed significantly in males but were mostly unaffected in females. In females 18 of 35 remaining parameters (51%) and in males 22 parameters (63%) changed significantly between spatial resolutions. This work represents the first step in studying the impact of video resolution on quantitative HSV parameters. Clear influences of spatial camera resolution on computed parameters were found. The study results suggest avoiding the use of the most strongly affected parameters. Further, the use of cameras with high resolution is recommended to analyze GAW measures in HSV data.

Published
2019
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8. Towards a Clinically Applicable Computational Larynx Model

Author

Hossein Sadeghi, Stefan Kniesburges, Sebastian Falk, Manfred Kaltenbacher, Anne Schützenberger, and Michael Döllinger

Subjects
numerical larynx model, clinical potential, glottal aerodynamics, computational cost, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

The enormous computational power and time required for simulating the complex phonation process preclude the effective clinical use of computational larynx models. The aim of this study was to evaluate the potential of a numerical larynx model, considering the computational time and resources required. Using Large Eddy Simulations (LES) in a 3D numerical larynx model with prescribed motion of vocal folds, the complicated fluid-structure interaction problem in phonation was reduced to a pure flow simulation with moving boundaries. The simulated laryngeal flow field is in good agreement with the experimental results obtained from authors’ synthetic larynx model. By systematically decreasing the spatial and temporal resolutions of the numerical model and optimizing the computational resources of the simulations, the elapsed simulation time was reduced by 90% to less than 70 h for 10 oscillation cycles of the vocal folds. The proposed computational larynx model with reduced mesh resolution is still able to capture the essential laryngeal flow characteristics and produce results with sufficiently good accuracy in a significant shorter time-to-solution. The reduction in computational time achieved is a promising step towards the clinical application of these computational larynx models in the near future.

Published
2019
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9. Impact of Subharmonic and Aperiodic Laryngeal Dynamics on the Phonatory Process Analyzed in Ex Vivo Rabbit Models

Author

Fabian Thornton, Michael Döllinger, Stefan Kniesburges, David Berry, Christoph Alexiou, and Anne Schützenberger

Subjects
ex vivo phonation, rabbit model, aperiodic dynamics, subharmonic dynamics, high-speed digital imaging, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Normal voice is characterized by periodic oscillations of the vocal folds. On the other hand, disordered voice dynamics (e.g., subharmonic and aperiodic oscillations) are often associated with voice pathologies and dysphonia. Unfortunately, not all investigations may be conducted on human subjects; hence animal laryngeal studies have been performed for many years to better understand human phonation. The rabbit larynx has been shown to be a potential model of the human larynx. Despite this fact, only a few studies regarding the phonatory parameters of rabbit larynges have been performed. Further, to the best of our knowledge, no ex vivo study has systematically investigated phonatory parameters from high-speed, audio and subglottal pressure data with irregular oscillations. To remedy this, the present study analyzes experiments with sustained phonation in 11 ex vivo rabbit larynges for 51 conditions of disordered vocal fold dynamics. (1) The results of this study support previous findings on non-disordered data, that the stronger the glottal closure insufficiency is during phonation, the worse the phonatory characteristics are; (2) aperiodic oscillations showed worse phonatory results than subharmonic oscillations; (3) in the presence of both types of irregular vibrations, the voice quality (i.e., cepstral peak prominence) of the audio and subglottal signal greatly deteriorated compared to normal/periodic vibrations. In summary, our results suggest that the presence of both types of irregular vibration have a major impact on voice quality and should be considered along with glottal closure measures in medical diagnosis and treatment.

Published
2019
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10. Influence of Analyzed Sequence Length on Parameters in Laryngeal High-Speed Videoendoscopy

Author

Patrick Schlegel, Marion Semmler, Melda Kunduk, Michael Döllinger, Christopher Bohr, and Anne Schützenberger

Subjects
high-speed videoendoscopy, glottal area waveform, sequence length, parameters, diagnosis, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Laryngeal high-speed videoendoscopy (HSV) allows objective quantification of vocal fold vibratory characteristics. However, it is unknown how the analyzed sequence length affects some of the computed parameters. To examine if varying sequence lengths influence parameter calculation, 20 HSV recordings of healthy females during sustained phonation were investigated. The clinical prevalent Photron Fastcam MC2 camera with a frame rate of 4000 fps and a spatial resolution of 512 × 256 pixels was used to collect HSV data. The glottal area waveform (GAW), describing the increase and decrease of the area between the vocal folds during phonation, was extracted. Based on the GAW, 16 perturbation parameters were computed for sequences of 5, 10, 20, 50 and 100 consecutive cycles. Statistical analysis was performed using SPSS Statistics, version 21. Only three parameters (18.8%) were statistically significantly influenced by changing sequence lengths. Of these parameters, one changed until 10 cycles were reached, one until 20 cycles were reached and one, namely Amplitude Variability Index (AVI), changed between almost all groups of different sequence lengths. Moreover, visually observable, but not statistically significant, changes within parameters were observed. These changes were often most prominent between shorter sequence lengths. Hence, we suggest using a minimum sequence length of at least 20 cycles and discarding the parameter AVI.

Published
2018
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11. Endoscopic Laser-Based 3D Imaging for Functional Voice Diagnostics

Author

Marion Semmler, Stefan Kniesburges, Jonas Parchent, Bernhard Jakubaß, Maik Zimmermann, Christopher Bohr, Anne Schützenberger, and Michael Döllinger

Subjects
3D imaging, endoscopy, laser projection, high-speed imaging, automation, vocal folds, larynx, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Recently, we reported on the in vivo application of a miniaturized measuring device for 3D visualization of the superior vocal fold vibrations from high-speed recordings in combination with a laser projection unit (LPU). As a long-term vision for this proof of principle, we strive to integrate the further developed laserendoscopy as a diagnostic method in daily clinical routine. The new LPU mainly comprises a Nd:YAG laser source (532 nm/CW/2 ω ) and a diffractive optical element (DOE) generating a regular laser grid (31 × 31 laser points) that is projected on the vocal folds. By means of stereo triangulation, the 3D coordinates of the laser points are reconstructed from the endoscopic high-speed footage. The new design of the laserendoscope constitutes a compromise between robust image processing and laser safety regulations. The algorithms for calibration and analysis are now optimized with respect to their overall duration and the number of required interactions, which is objectively assessed using binary classifiers. The sensitivity and specificity of the calibration procedure are increased by 40.1% and 22.3%, which is statistically significant. The overall duration for the laser point detection is reduced by 41.9%. The suggested semi-automatic reconstruction software represents an important stepping-stone towards potential real time processing and a comprehensive, objective diagnostic tool of evidence-based medicine.

Published
2017
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13. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials

Author

Charles C Wykoff, Francis Abreu, Anthony P Adamis, Karen Basu, David A Eichenbaum, Zdenka Haskova, Hugh Lin, Anat Loewenstein, Shaun Mohan, Ian A Pearce, Taiji Sakamoto, Patricio G Schlottmann, David Silverman, Jennifer K Sun, John A Wells, Jeffrey R Willis, Ramin Tadayoni, Thomas Aaberg, Ashkan Abbey, Elmira Abdulaeva, Santiago Abengoechea, Prema Abraham, Thomas Ach, Serrhel Adams, Alfredo Adan Civera, Sean Adrean, Hansjurgen Agostini, Suhail Alam, Arturo Alezzandrini, Virgil Alfaro, Daniel Aliseda, Arghavan Almony, Pedro Amat, Payam Amini, Andrew Antoszyk, Luis Arias, Riaz Asaria, Marcos Avila, Carl C Awh, Joaquin Bafalluy, Carl Baker, Francesco Bandello, Mark Barakat, Karen Barraza, Gyorgy Bator, Caroline Baumal, Rubens Belfort Jr, Chris Bergstrom, George Bertolucci, Thomas Bochow, Matthias Bolz, Emilia Borcz, Arnaldo Bordon, David Boyer, Galina Bratko, Michael Brent, Jamin Brown, David M Brown, Maria Budzinskaya, Sylvia Buffet, Stuart Burgess, Ben Burton, Miguel Busquets, Francisco Cabrera, Carlo Cagini, Jorge Calzada, Peter Campochiaro, John Carlson, Alessandro Castellarin, Carlos Cava, Voraporn Chaikitmongkol, Clement Chan, Emmanuel Chang, Jonathan Chang, Andrew Chang, Steve Charles, Nauman Chaudhry, Caroline Chee, Judy Chen, Fred Chen, Shih-Jen Chen, Richard Cheong-Leen, Allen Chiang, Mark Chittum, David Chow, Brian Connolly, Pierre Loic Cornut, Karl Csaky, Carl Danzig, Arup Das, Vesselin Daskalov, Carmen Desco, Amr Dessouki, John Dickinson, Brian Do, Michael Dollin, Pravin Dugel, Jaroslava Dusova, David Eichenbaum, Bora Eldem, Robert Engstrom, Jan Ernest, Joan Josep Escobar, Simona Esposti, Nicole Eter, Naomi Falk, Andrej Farkas, Leonard Feiner, Nicolas Feltgen, Carlos Fernandez, Alvaro Fernandez Vega, Philip Ferrone, Joao Figueira, Marta Figueroa, Oliver Findl, Howard Fine, Jorge Fortun, Gregory M Fox, Scott Foxman, Carsten Framme, Samantha Fraser-Bell, Arthur Fu, Akira Fukutomi, Nicholas Fung, Federico Furno Sola, Roberto Gallego-Pinazo, Renata Garcia, Alfredo Garcia-Layana, Maciej Gawecki, Sheen George, Faruque Ghanchi, Ghassan Ghorayeb, Roger Goldberg, Michaella Goldstein, Nuno Gomes, Francisco Gomez Ulla, Victor Gonzalez, Craig Greven, Sunil Gupta, Miguel Guzman, Martin Harris, Katja Hatz, Vivienne Hau, Vincent Hau, Ken Hayashi, Jeffrey Heier, Ewa Herba, Vrinda Hershberger, Patrick Higgins, Akito Hirakata, Allen Ho, Nancy Holekamp, Shigeru Honda, Jason Hsu, Allen Hu, Maria Hurcikova, Yasuhiro Ikeda, Ricky Isernhagen, Yasuki Ito, Tim Jackson, Rachael Jacoby, Afsar Jafree, Golnaz Javey, Cameron Javid, Chirag Jhaveri, Mark Johnson, Marek Kacerík, Jakub Kaluzny, Daniel Kampik, Se Woong Kang, Kapil Kapoor, Levent Karabas, Tsutomu Kawasaki, Agnes Kerenyi, Arshad Khanani, Rahul Khurana, Brian Kim, Kazuhiro Kimura, Genichiro Kishino, Shigehiko Kitano, Kendra Klein-Mascia, Gregg Kokame, Jean Francois Korobelnik, Alexey Kulikov, Ajay Kuriyan, Henry Kwong, Robert Kwun, Timothy Lai, Chi-Chun Lai, Philip Laird, Laurent Lalonde, Paolo Lanzetta, Michael Larsen, Caroline Laugesen, Daniel Lavinsky, Olivier Lebreton, Seong Lee, Jaime Levy, Blandina Lipkova, Mimi Liu, Judy Liu, Chris P Lohmann, Nikolas London, Katrin Lorenz, Andrew Lotery, David Lozano Rechy, Silvio Lujan, Patrick Ma, Takatoshi Maeno, Sajjad Mahmood, Fuad Makkouk, Khurram Malik, Dennis Marcus, Alan Margherio, Leonardo Mastropasqua, Raj Maturi, Frank McCabe, Martin McKibbin, Hemal Mehta, Geeta Menon, Jale Mentes, Katarzyna Michalska-Malecka, Aneta Misheva, Yoshinori Mitamura, Paul Mitchell, Yasha Modi, Quresh Mohamed, Javier Montero, Jeffrey Moore, Virgilio Morales Canton, Haia Morori-Katz, Tatiana Morugova, Tomoaki Murakami, Maria Muzyka-Wozniak, Marco Nardi, Jan Nemcansky, Kamila Nester-Ostrowska, Julio Neto, Charles Newell, Massimo Nicolo, Jared Nielsen, Kousuke Noda, Akira Obana, Nahoko Ogata, Hideyasu Oh, Kean Oh, Matthew Ohr, Piotr Oleksy, Scott Oliver, Sebastien Olivier, James Osher, Sehnaz Ozcalişkan, Banu Ozturk, Andras Papp, Kyu Hyung Park, D Wilkin Parke, Maria Cristina Parravano, Sugat Patel, Sunil Patel, Ian Pearce, Joel Pearlman, Fernando Penha, Irfan Perente, Stephen Perkins, Grazia Pertile, Iva Petkova, Tunde Peto, Dante Pieramici, Andreas Pollreisz, Pear Pongsachareonnont, Nadezhda Pozdeyeva, Siegfried Priglinger, Jawad Qureshi, Dorota Raczynska, Rajesh Rajagopalan, Juan Ramirez Estudillo, Paul Raskauskas, Rajiv Rathod, Hessam Razavi, Carl Regillo, Federico Ricci, Soraya Rofagha, Dominika Romanczak, Bożena Romanowska-Dixon, Daniel Rosberger, Irit Rosenblatt, Brett Rosenblatt, Adam Ross, Paisan Ruamviboonsuk, Jose Maria Ruiz Moreno, Gustavo Salomão, Sukhpal Sandhu, Dirk Sandner, Laura Sararols, Osamu Sawada, Ramin Schadlu, Patricio Schlottmann, Claudia Schuart, Berthold Seitz, András Seres, Figen Sermet, Sandeep Shah, Ankur Shah, Rohan Shah, Sumit Sharma, Thomas Sheidow, Veeral Sheth, Akito Shimouchi, Masahiko Shimura, Bartosz Sikorski, Rufino Silva, Michael Singer, Lawrence Singerman, Rishi Singh, Eric Souied, David J Spinak, Georg Spital, Nathan Steinle, Jeffrey Stern, Glenn Stoller, Robert Stoltz, Cameron Stone, Amy Stone, Eric Suan, Masahiko Sugimoto, Iichiro Sugita, Jennifer Sun, Xiaodong Sun, Ivan Suner, Lajos Szalczer, Timea Szecsko, Ali Tabassian, Hitoshi Takagi, Kei Takayama, Alexandre Taleb, James Talks, Gavin Tan, Teruyo Tanabe, Stanford Taylor, Allen Thach, John Thompson, Paul Tlucek, Robert Torti, Daniela Tosheva Guneva, Edit Toth-Molnar, Eduardo Uchiyama, Attila Vajas, Deepali Varma, Balazs Varsanyi, Petja Vassileva, Sara Vaz-Pereira, Miroslav Veith, Jose Ignacio Vela, Francesco Viola, Gianni Virgili, Gábor Vogt, Henrik Vorum, Pamela Weber, Thoalf Wecke, Raymond Wee, Martin Weger, Paul Weishaar, Sanjeewa Wickremasinghe, Thomas Reginald Williams, Thomas Williams, Geoff Williams, Armin Wolf, Jeremy Wolfe, James Wong, David Wong, Ian Wong, Robert Wong, Bogumil Wowra, Edward Wylęgała, Chang-Hao Yang, Tsutomu Yasukawa, Paul Yates, Gursel Yilmaz, Glenn Yiu, Young Hee Yoon, Barak Yoreh, Shigeo Yoshida, Hyeong Gon Yu, Seung Young Yu, Tatiana Yurieva, Leandro Zacharias, Karolina Zaczek Zakrzewska, Alberto Zambrano, Barbara Zatorska, Carlos Zeolite, and Jeffrey Zheutlin

Subjects
Male, Vascular Endothelial Growth Factor A, Diabetic Retinopathy, Recombinant Fusion Proteins, Visual Acuity, Angiogenesis Inhibitors, General Medicine, Middle Aged, Drug Administration Schedule, Angiopoietin-2, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, Double-Blind Method, Antibodies, Bispecific, Intravitreal Injections, Edema, Humans, Female, Macula Lutea, Aged
Abstract

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

Published
2022
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14. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials

Author

Jeffrey S Heier, Arshad M Khanani, Carlos Quezada Ruiz, Karen Basu, Philip J Ferrone, Christopher Brittain, Marta S Figueroa, Hugh Lin, Frank G Holz, Vaibhavi Patel, Timothy Y Y Lai, David Silverman, Carl Regillo, Balakumar Swaminathan, Francesco Viola, Chui Ming Gemmy Cheung, Tien Y Wong, Ashkan Abbey, Elmira Abdulaeva, Prema Abraham, Alfredo Adan Civera, Hansjurgen Agostini, Arturo Alezzandrini, Virgil Alfaro, Arghavan Almony, Lebriz Altay, Payam Amini, Andrew Antoszyk, Etelka Aradi, Luis Arias, Jennifer Arnold, Riaz Asaria, Sergei Astakhov, Yury Astakhov, Carl C. Awh, Chandra Balaratnasingam, Sanjiv Banerjee, Caroline Baumal, Matthias Becker, Rubens Belfort, Galina Bratko, William Jr. Z Bridges, Jamin Brown, David M. Brown, Maria Budzinskaya, Sylvia Buffet, Stuart Burgess, Iksoo Byon, Carlo Cagini, Jorge Calzada, Stone Cameron, Peter Campochiaro, John Carlson, Angela Carneiro, Clement Chan, Emmanuel Chang, Andrew Chang, Daniel Chao, Nauman Chaudhry, Caroline Chee, Andrew Cheek, Shih-Jen Chen, San-Ni Chen, Gemmy Cheung, Saradha Chexal, Mark Chittum, David Chow, Abosede Cole, Brian Connolly, Pierre Loic Cornut, Stephen Couvillion, Carl Danzig, Vesselin Daskalov, Amr Dessouki, Francois Devin, Michael Dollin, Rosa Dolz, Louise Downey, Richard Dreyer, Pravin Dugel, David Eichenbaum, Bora Eldem, Robert Engstrom, Joan Josep Escobar, Nicole Eter, David W. Faber, Naomi Falk, Leonard Feiner, Alvaro Fernandez Vega, Philip Ferrone, Marta Figueroa, Howard Fine, Mitchell Fineman, Gregory M. Fox, Catherine Francais, Pablo Franco, Samantha Fraser-Bell, Nicholas Fung, Federico Furno Sola, Richard Gale, Alfredo Garcia-Layana, Julie Gasperini, Maciej Gawecki, Faruque Ghanchi, Manjot Gill, Michel Giunta, David Glaser, Michaella Goldstein, Francisco Gomez Ulla, Fumi Gomi, Victor Gonzalez, Jordan Graff, Sunil Gupta, Rainer Guthoff, Robyn Guymer, Anton Haas, Robert Hampton, Katja Hatz, Ken Hayashi, Jeffrey Heier, Ewa Herba, Vrinda Hershberger, Patrick Higgins, Nancy Holekamp, Shigeru Honda, James Howard, Allen Hu, Stephen Huddleston, Tomohiro Iida, Hiroko Imaizumi, Yasuo Ito, Yasuki Ito, Sujit Itty, Golnaz Javey, Cameron Javid, Tatsushi Kaga, Jakub Kaluzny, Se Woong Kang, Kapil Kapoor, Levent Karabas, Tsutomu Kawasaki, Patrick Kelty, Agnes Kerenyi, Arshad Khanani, Ramin Khoramnia, Rahul Khurana, Kazuhiro Kimura, Kendra Klein-Mascia, Namie Kobayashi, Laurent Kodjikian, Hideki Koizumi, Gregg Kokame, Alexey Kulikov, Henry Kwong, Robert Kwun, Timothy Lai, Chi-Chun Lai, Laurent Lalonde, Paolo Lanzetta, Michael Larsen, Adrian Lavina, Won Ki Lee, ji Eun Lee, Seong Lee, Jaime Levy, Lucas Lindsell, Mimi Liu, Nikolas London, Andrew Lotery, David Lozano Rechy, Alan Luckie, David Maberley, Takatoshi Maeno, Sajjad Mahmood, Fuad Makkouk, Dennis Marcus, Alan Margherio, Helene Masse, Hisashi Matsubara, Raj Maturi, Sonia Mehta, Geeta Menon, Jale Mentes, Mark Michels, Yoshinori Mitamura, Paul Mitchell, Quresh Mohamed, Jordi Mones, Rodrigo Montemayor Lobo, Javier Montero, Jeffrey Moore, Ryusaburo Mori, Haia Morori-Katz, Raj Mukherjee, Toshinori Murata, Maria Muzyka-Wozniak, Marco Nardi, Niro Narendran, Massimo Nicolo, Jared Nielsen, Tetsuya Nishimura, Kousuke Noda, Anna Nowinska, Hideyasu Oh, Matthew Ohr, Annabelle Okada, Piotr Oleksy, Shinji Ono, Sengul Ozdek, Banu Ozturk, Luis Pablo, Kyu Hyung Park, D. Wilki Parke, Maria Cristina Parravano, Praveen Patel, Apurva Patel, Sunil Patel, Sugat Patel, Daniel Pauleikhoff, Ian Pearce, Joel Pearlman, Iva Petkova, Dante Pieramici, Nadezhda Pozdeyeva, Jawad Qureshi, Dorota Raczynska, Juan Ramirez Estudillo, Rajiv Rathod, Hessam Razavi, Gayatri Reilly, Federico Ricci, Ryan Rich, Bożena Romanowska-Dixon, Irit Rosenblatt, Jose Maria Ruiz Moreno, Stefan Sacu, Habiba Saedon, Usman Saeed, Min Sagong, Taiji Sakamoto, Sukhpal Sandhu, Laura Sararols, Mario Saravia, Ramin Schadlu, Patricio Schlottmann, Tetsuju Sekiryu, András Seres, Figen Sermet, Sumit Shah, Rohan Shah, Ankur Shah, Thomas Sheidow, Veeral Sheth, Chieko Shiragami, Bartosz Sikorski, Rufino Silva, Lawrence Singerman, Robert Sisk, Torben L. Sørensen, Eric Souied, David-J Spinak, Giovanni Staurenghi, Robert Steinmetz, Glenn Stoller, Robert Stoltz, Eric Suan, Ivan Suner, Yzer Suzanne, Ramin Tadayoni, Kanji Takahashi, Kei Takayama, Alexandre Taleb, James Talks, Hiroko Terasaki, John Thompson, Edit Toth-Molnar, Khoi Tran, Raman Tuli, Eduardo Uchiyama, Attila Vajas, Janneke Van Lith-Verhoeven, Balazs Varsanyi, Gianni Virgili, Gábor Vogt, Michael Völker, David Warrow, Pamela Weber, John A. Wells, Sanjeewa Wickremasinghe, Mark Wieland, Geoff Williams, Thomas Williams, David Wong, King Wong, James Wong, Ian Wong, Robert Wong, Bogumil Wowra, Charles C. Wykoff, Ayana Yamashita, Kanako Yasuda, Gursel Yilmaz, Glenn Yiu, Ai Yoneda, Young Hee Yoon, Barak Yoreh, HyeongGon Yu, Seung Young Yu, Tatiana Yurieva, Alberto Zambrano, Barbara Zatorska, and Carlos Zeolite

Subjects
Aged, 80 and over, Male, Vascular Endothelial Growth Factor A, Recombinant Fusion Proteins, Visual Acuity, Angiogenesis Inhibitors, General Medicine, Drug Administration Schedule, Angiopoietin-2, Macular Degeneration, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, Double-Blind Method, Antibodies, Bispecific, Intravitreal Injections, Humans, Female, Aged
Abstract

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

Published
2022
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15. Biomechanics of sound production in high-pitched classical singing

Author

Matthias Echternach, Fabian Burk, Marie Köberlein, Michael Döllinger, Michael Burdumy, Bernhard Richter, Ingo R. Titze, Coen P. H. Elemans, and Christian T. Herbst

Subjects
Medicine, Science
Abstract

Abstract Voice production of humans and most mammals is governed by the MyoElastic-AeroDynamic (MEAD) principle, where an air stream is modulated by self-sustained vocal fold oscillation to generate audible air pressure fluctuations. An alternative mechanism is found in ultrasonic vocalizations of rodents, which are established by an aeroacoustic (AA) phenomenon without vibration of laryngeal tissue. Previously, some authors argued that high-pitched human vocalization is also produced by the AA principle. Here, we investigate the so-called “whistle register” voice production in nine professional female operatic sopranos singing a scale from C6 (≈ 1047 Hz) to G6 (≈ 1568 Hz). Super-high-speed videolaryngoscopy revealed vocal fold collision in all participants, with closed quotients from 30 to 73%. Computational modeling showed that the biomechanical requirements to produce such high-pitched voice would be an increased contraction of the cricothyroid muscle, vocal fold strain of about 50%, and high subglottal pressure. Our data suggest that high-pitched operatic soprano singing uses the MEAD mechanism. Consequently, the commonly used term “whistle register” does not reflect the physical principle of a whistle with regard to voice generation in high pitched classical singing.

Published
2024
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16. Vision-Related Quality of Life in Patients with Diabetic Macular Edema Treated with Intravitreal Aflibercept

Author

Justus G. Garweg, Jana Stefanickova, Carel Hoyng, Thomas Schmelter, Tobias Niesen, Olaf Sowade, Sobha Sivaprasad, Alfredo Adan, Mikulas Alexik, Fareed Ali, Miguel Amaro, Vilma-Jurate Balciuniene, Francesco M. Bandello, Lluis Arias Barquet, Anna Beck, Katharina Bell, Francesco Boscia, Anniken Bures, Ângela Carneiro, David R. Chow, Andrius Cimbalas, Claudia Dahlke, Varma Deepali, John D. Dickinson, Michael Dollin, Chiara Eandi, Karl-Heinz Emmerich, Nicolas Feltgen, João Pereira Figueira, Oliver Findl, Monika Gajdošová, Richard P. Gale, Ivan John Galic, Justus Garweg, Vanessa Gasser-Steiner, Michel Giunta, John R. Gonder, Andrzej Grzybowski, Jan Hamouz, Lars-Olof Hattenbach, Frank G. Holz, Hasan Jesia, Jozef Kaluzny, Agnes Kerenyi, Peter J. Kertes, Frank Koch, Laurent Kodjikan, David E. Lederer, Ivana Liehneova, Katrin Lorenz, Andrew J. Lotery, Martin McKibbin, Geeta V. Menon, Zofia Michalewska, Edoardo Midena, Massimo Nicolo, Andras Papp, Gabriela Pavlovičová, Enrico Peiretti, Sara Vaz-Pereira, Paolo Perri, Ioannis Petropoulos, Frederic Queguiner, Krystyna Raczynska, Laura Sararols-Ramsay, Marek Rękas, Federico Ricci, Bozena Romanowska-Dixon, Helmut G. Sachs, Saddek Mohand-Said, Dirk Sandner, Ursula Schmidt-Erfurth, Walter Sekundo, Andras Seres, Eric Souied, João Castro de Sousa, Andrzej Stankiewicz, Jana Štefaničková, Katarína Struhárová, Jan Studnicka, Enrique Cervera Taulet, Simon Taylor, Slawomir Teper, Attila Vajas, Carlos Cava Valenciano, Balázs Varsányi, Francesco Viola, Gianni Virgili, Lars Wagenfeld, Gavin Walters, Peter Wiedemann, and Tomasz Zarnowski

Subjects
medicine.medical_specialty, Visual acuity, genetic structures, law.invention, 03 medical and health sciences, 0302 clinical medicine, Endophthalmitis, Randomized controlled trial, Quality of life, law, Ophthalmology, Diabetes mellitus, Medicine, Adverse effect, 030304 developmental biology, Aflibercept, 0303 health sciences, business.industry, Diabetic retinopathy, medicine.disease, eye diseases, 030221 ophthalmology & optometry, medicine.symptom, business, medicine.drug
Abstract

Purpose To examine vision-related quality of life in patients with diabetic macular edema (DME) treated with intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY). Design AQUA was a multicenter, open-label, single-arm, phase 4 study. Participants Adults 18 years of age or older with type 1 or 2 diabetes mellitus and DME. Methods Patients received intravitreal aflibercept 2 mg every 8 weeks for 52 weeks, after 5 initial doses every 4 weeks. Main Outcome Measures The primary outcome was the change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) total score from baseline to week 52. Secondary outcomes included the change in NEI VFQ-25 near and distant activities subscale scores, best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and central retinal thickness (CRT) from baseline to week 52. Change in NEI VFQ-25 score at week 52 for better-seeing eyes (BSEs) and worse-seeing eyes (WSEs) also was evaluated. Results A total of 553 patients comprised the full analysis set, and 560 patients comprised the safety analysis set. At baseline, the mean NEI VFQ-25 total score was 70.12, mean BCVA was 61.5 ETDRS letters, and mean CRT was 464.81 μm. A mean of 8.8 injections were administered over 52 weeks. At week 52, the mean improvement from baseline in the NEI VFQ-25 total score was +6.11 (standard deviation [SD], 11.46); the corresponding improvements in near and distant activities were +11.37 (SD, 18.01) and +7.33 (SD, 17.32), respectively. Similarly, improvements in patients whose BSE and WSE were treated were 7.74 (SD, 13.59) and 5.48 (SD, 9.70), respectively. At week 52, mean change in BCVA was +10.0 ETDRS letters (SD, 8.0 ETDRS letters), and mean change in CRT was –175.38 μm (SD, 132.62 μm). Overall, 53.6% of patients reported treatment-emergent adverse events (TEAEs), of whom 26.8% experienced an ocular TEAE in the study eye. The most common serious ocular TEAE was endophthalmitis (0.5% [n = 3]). Five deaths (0.9%) were reported, but were not considered treatment related. Conclusions Intravitreal aflibercept was associated with clinically meaningful improvements in NEI VFQ-25 total score over 52 weeks in patients with DME; these were even more pronounced for near than for distant activities. Adverse events were consistent with the known safety profile of intravitreal aflibercept.

Published
2019
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17. 3D reconstruction of vocal fold dynamics with laser high‐speed videoendoscopy in children

Author

Rita R. Patel, Michael Döllinger, and Marion Semmler

Subjects
high‐speed videoendoscopy, laser endoscopy, pediatrics, three‐dimensional imaging, Otorhinolaryngology, RF1-547, Surgery, RD1-811
Abstract

Abstract Objective The objective of this study is to evaluate three‐dimensional vertical motion of the superior surface of the vocal folds in vivo in (a) typically developing children as a function of vocal frequency variations and (b) a child with vocal nodules. Methods A custom developed laser endoscope coupled with high‐speed videoendoscopy was used to obtain 3D parameters from 2 healthy children, one child with vocal nodules, and 23 vocally healthy adults (females = 11, males = 12). Parameters of amplitude (mm), maximum opening/closing velocity (mm/s), and mean opening/closing velocity (mm/s) were computed for the lateral and vertical vibratory motion along the anterior, middle, and posterior sections of the vocal folds were computed. Results We provide for the first time, absolute measurements of vertical amplitude and maximum/ mean velocity during the opening and closing phases, in vivo in children. Overall, the vertical motion was larger in vocally normal children compared with the lateral motion, especially along the visible posterior section of the vocal folds and during low pitch phonation. The opening phase dynamics were consistently large along the posterior section in the child with vocal nodules. Conclusions The study findings establish the feasibility of capturing 3D motion in a clinical setting and provide proof of concept for the application of the proposed 3D laser in the pediatric population. Future large sample size studies are needed to establish the diagnostic potential of examining the closing phase vertical motion to evaluate vibratory development in children with normal voice and investigating the opening phase vertical motion in children with nodules. Level of Evidence N/A.

Published
2024
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18. VOAT: Voice Onset Analysis Tool

Author

Tomás Arias-Vergara, Catherine Madill, Duong Nguyen, John Holik, and Michael Döllinger

Subjects
Onset of phonation, Voice analysis, Phonation onset time, Biomarker, Computer software, QA76.75-76.765
Abstract

The onset of phonation can be used as a biomarker for quantitative voice assessment and identification of phonation type, e.g., breathy, modal, and creaky. The onset of phonation can be calculated considering different modalities: acoustic, electroglottography (EGG), airflow, and glottal area waveforms. Considering the potential of voice onset in clinical applications, we have been developing the Voice Onset Analysis Tool (VOAT), a computer-aided program written in Python for the semi-automatic detection of vowel phonation onset. VOAT can detect the vowel onset on recordings with multiple phonations. Furthermore, the user can manually select the segments from the recording where the onset is present or apply a voice activity detection for automatic segmentation. VOAT provides filtering options to facilitate the detection and allows the saving of results in an Excel file for further processing. Our software also allows batch processing to detect vowel onset on several files automatically.

Published
2024
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19. Needle-Guided Intraoperative Iridectomy During Vitreoretinal Surgery

Author

André S. Pollmann, Michael Dollin, Amit V. Mishra, R. Rishi Gupta, and Ashley Whelan

Subjects
medicine.medical_specialty, business.industry, Ophthalmology, Iridectomy, medicine.medical_treatment, Medicine, Vitreoretinal surgery, business, Special Correspondence
Published
2021

20. Inner Retinal Morphology and Visual Outcomes in Idiopathic Epiretinal Membrane Surgery: A Retrospective Optical Coherence Tomography Study

Author

Michael Dollin and Ioannis S. Dimopoulos

Subjects
0301 basic medicine, Retina, medicine.medical_specialty, genetic structures, medicine.diagnostic_test, business.industry, Retinal, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Optical coherence tomography, chemistry, Ophthalmology, 030221 ophthalmology & optometry, Medicine, Original Manuscripts, Epiretinal membrane, business
Abstract

Purpose: Epiretinal membrane (ERM) is a common retinal finding for patients older than 50 years. Disorganization of the retinal inner layers (DRIL) has emerged as a novel predictor of poor visual acuity (VA) in eyes with inner retinal pathology. The aim of our study is to correlate preoperative DRIL with visual outcomes after ERM surgery. Methods: Medical records and optical coherence tomography (OCT) images of 81 pseudophakic patients who underwent treatment of idiopathic ERM were reviewed. Preoperative DRIL on OCT was correlated with VA at baseline and at 3 and 6 months after ERM surgery. DRIL was defined as the loss of distinction between the ganglion cell–inner plexiform layer complex, inner nuclear layer, and outer plexiform layer. DRIL severity was based on its extent within the central 2-mm region of a transfoveal B-scan (absent/mild: one-third horizontal width). Results: Review of preoperative OCT showed severe DRIL in 41% and absent/mild DRIL in 59%. Severe DRIL was associated with worse baseline VA ( P < .001). Preoperative VA and DRIL status at baseline were both predictors of postoperative VA at follow-up time points ( P < .001). Severe DRIL was associated with significantly less improvement in VA at 6 months (–0.23 logMAR for absent/mild vs –0.14 for severe DRIL). Conclusions: Presence of severe preoperative DRIL correlates with worse baseline VA in patients with ERM and reduced VA improvement at 6 months. DRIL can be a strong predictor of long-term poor visual outcomes in ERM surgery.

Published
2021

21. Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration

Author

Jeannette J. Yu, Elvira Agrón, Traci E. Clemons, Amitha Domalpally, Freekje van Asten, Tiarnan D. Keenan, Catherine Cukras, Emily Y. Chew, Frederick L. Ferris, John Paul SanGiovanni, Traci Clemons, Anne Lindblad, Robert Lindblad, Nilay Shah, Robert Sperduto, Wendy McBee, Gary Gensler, Molly Harrington, Alice Henning, Katrina Jones, Kumar Thotapally, Diana Tull, Valerie Watson, Kayla Williams, Christina Gentry, Francine Kaufman, Chris Morrison, Elizabeth Saverino, Sherrie Schenning, Barbara Blodi, Ronald P. Danis, Matthew Davis, Kathy Glander, Gregory Guilfoil, Larry D. Hubbard, Kristine Johnson, Ronald Klein, Barbara Nardi, Michael Neider, Nancy Robinson, Eileen Rosensteel, Hugh Wabers, Grace Zhang, Alan J. Ruby, Antonio Capone, Bawa Dass, Kimberly Drenser, Bruce R. Garretson, Tarek S. Hassan, Michael Trese, George A. Williams, Jeremy Wolfe, Tina Bell, Mary Zajechowski, Dennis Bezaire, Fran McIver, Anthony Medina, Jackie Pagett, Stephanie Hatch Smith, Lynn Swartz, Tom Treuter, Andrew Antoszyk, Justin Brown, David J. Browning, Walter Holland, Angella Karow, Kelly Stalford, Angela Price, Sarah Ennis, Sherry Fredenberg, Jenna Herby, Uma Balasubramaniam, Loraine Clark, Donna McClain, Michael McOwen, Lynn Watson, Michael Klein, Steven T. Bailey, Thomas J. Hwang, Andreas Lauer, J. Timothy Stout, Patty McCollum, Milt Johnson, Patrick B. Rice, Ivana Kim, John Loewenstein, Joan Miller, Lucia Sobrin, Lucy Young, Jacqueline Sullivan, Patricia Houlihan, Linda Merry, Ann Marie Lane, Ursula Lord Bator, Claudia Evans, Sarah Brett, Charleen Callahan, Marcia Grillo, David Walsh, Kamella Lau Zimmerman, Gary Edd Fish, Rajiv Anand, Lori E. Coors, Dwain G. Fuller, Rand Spencer, Robert C. Wang, Karen Duignan, Sally Arceneaux, Hank Aguado, Nicholas Hesse, Michael Mackens, Brian Swan, Wai T. Wong, Monica Dalal, Naima Jacobs-El, Catherine Meyerle, Benjamin Nicholson, Henry Wiley, Katherine Hall Shimel, Angel Garced, Janice Oparah, Greg Short, Alana Temple, Babilonia Ayukawa, Guy Foster, Darryl Hayes, Dessie Koutsandreas, Roula Nashwinter, John Rowan, Michael Bono, Denise Cunningham, Marilois Palmer, Alicia Zetina, David H. Orth, Kourous Rezaei, Joseph Civantos, Sohail Hasan, Kirk Packo, Celeste Figliulo, Pam Stanberry, Tara Farmer, Kiersten Nelson, Shannya Townsend-Patrick, Philip Rosenfeld, Royce Chen, Rishi Doshi, Sander Dubovy, Brian T. Kim, Matthew Lowrance, Andrew Moshfeghi, Zayna Nahas, Gary Schienbaum, John Vishak, Christina Weng, Zohar Yehoshua, Belen Rodriguez, Jose Rebimbas, Jane Gleichauf, Mike Kicak, Jason Mena, Tim Odem, Elizabeth Sferza-Camp, Alicia Disgdiertt, Jim Oramas, Isabel Rams, Stephanie Thatcher, Susan B. Bressler, Neil M. Bressler, Daniel Finkelstein, Steven H. Sherman, Sharon Solomon, Howard S. Ying, Rita Denbow, Deborah Phillips, Elizabeth Radcliffe, Judy Belt, Dennis Cain, David Emmert, Mark Herring, Jacquelyn McDonald, G. Baker Hubbard, Chris S. Bergstrom, Blaine Cribbs, Andrew Hendrick, Brandon Johnson, Philip Laird, Sonia Mehta, Timothy Olsen, Justin Townsend, Jion Yan, Steven Yeh, Linda Curtis, Judy Brower, Hannah Yi, Jannah Rutter Dobbs, Debbie Jordan, Michael J. Elman, Robert A. Liss, JoAnn Starr, Jennifer Belz, Charlene Putzulo, Teresa Coffey, Ashley Davis, Pamela Singletary, Giorya Shabi Andreani, Theresa Cain, Daniel Ketner, Peter Sotirakos, Suresh Chandra, Barbara A. Blodi, Michael M. Altaweel, Justin L. Gottlieb, Michael Ip, T. Michael Nork, Thomas S. Stevens, Kathryn Burke, Shelly Olson, Kristine Dietzman, Barbara Soderling, Guy Somers, Angie Wealti, Denise Krolnik, John Peterson, Sandra Reed, Thomas Friberg, Andrew Eller, Denise Gallagher, Leanne Labriola, Melissa Pokrifka, Aron Gedansky, Natalie Anthony, Cassandra Grzybowski, Dawn Matthews, Sharon Murajda-Jumba, Jessica Toro, David G. Callanan, Wayne A. Solley, Patrick Williams, Sandy Lash, Bob Boleman, Chris Dock, Michel Shami, Brenda Arrington, Ashaki Meeks, Alan R. Margherio, Paul Raphaelian, Debra Markus, Justin Langdon, Elizabeth Truax, Sandy Lewis, Brad Terry, Amy Noffke, Kean Oh, Ramin Sarrafizadeh, Scott Sneed, Julie Hammersley, Serena Neal, Mary Doran, Nan Jones, Lisa Preston, Heather Jessick, Tanya Tracy Marsh, Michael Tolentino, Adam Berger, Richard Hamilton, David Misch, Suk Jin Moon, Dawn Sutherland, Vera Dilts, Sara Henderson, Esmeralda Medina, Donald Trueman, Laura Holm, Jason Strickland, Darmakusuma Ie, Jeffrey L. Lipkowitz, Kekul B. Shah, Susan Geraghty, Beverly Sannazzaro, Morgan Harper, Krista Bayer, Mary B. Lansing, Lauren B. Fox, Rebecca Lee, Jay B. Stallman, Michael Jacobson, Sean Koh, Scott Lampert, John Miller, Mark Rivellese, Atul Sharma, Robert A. Stoltz, Stephanie Vanderveldt, Leslie Marcus, Starr Hendricks, Ryan Hollman, Grethel Betanzos, Leslie Ellorin, Shelly Fulbright, Debbie McCormick, Paul A. Edwards, Julianne Hall, Mary Monk, Melanie Gutkowski, Melina Mazurek, Janet Murphy, Katherine Gusas, Crystal Moffett, David Burley, Nicole Chesney, Katie Kilgo, Brian Rusinek, Bradley Stern, Tracy Troszak, Rhonda Baker-Levingston, Carl W. Baker, Tracey Caldwell, Tammy Walker, Lynnette F. Lambert, Tracey Martin, Mary Jill Palmer, Tana Williams, Michael A. Novak, Joseph Coney, David G. Miller, Scott Pendergast, Lawrence Singerman, Nicholas Zakov, Hernando Zegarra, Kim DuBois, Susan Rath, Lori Revella, Tammy Brink, Kim Drury, Lisa Hogue, Mary Ilc, Connie Keller, Elizabeth McNamara, Vivian Tanner, Tamara Cunningham, John DuBois, Gregg Greanoff, Trina Nitzsche, Sheila Smith-Brewer, Ricky D. Isernhagen, John W. Kitchens, Thomas W. Stone, William J. Wood, Diana Holcomb, Virginia Therrien, Michelle Buck, Jeanne Van Arsdall, Edward Slade, Todd E. Schneiderman, David J. Spinak, Jackie Gaedke, Heather Davis Brown, Dan Helgren, Jenifer Garrison Pangelinan, Lawrence Halperin, Scott Anagnoste, Mandeep Dhalla, Krista Rosenberg, Barry Taney, W. Scott Thompson, Jaclyn Lopez, Monica Hamlin, Monica Lopez, Jamie Mariano, Evelyn Quinchia, Patricia Aramayo, Rita Veksler, Michael Lee, Richard Dreyer, Irvin Handelman, Colin Ma, Mark Peters, Stephen Hobbs, Amanda Milliron, Marcia Kopfer, Michele Connaughton, A. Christine Hoerner, R. Joseph Logan, Harry J. Wohlsein, David Boyer, Thomas G. Chu, Pouya Dayani, David Liao, Roger L. Novack, Firas M. Rahhal, Richard Roe, Homayoun Tabandeh, Janet Bayramyan, Tammy Gasparyan, Connie Hoang, Janet Kurokouchi, Tammy Eileen Lo, Richard Ngo, Mary Ann Nguyen, Michael Peyton, Charles Yoon, Julio Sierra, Adam Zamboni, Jeff Kessinger, Eric Protacio, Adam Smucker, Pamela Rath, Robert Bergren, Bernard Doft, Judy Liu, Karl Olsen, Lori Merlotti, Willia Ingram, Kellianne Marfisi, Kimberly Yeckel, Heather Schultz Carmelo, Amanda Fec, Keith McBroom, David Steinberg, Marc Levy, Jody Abrams, Melvin Chen, Waldemar Torres, Peggy Jelemensky, Mark Prybylski, Tara Raphael, Diana Appleby, Charlotte Rodman, Mark Sneath, Robert H. Rosa, Vanessa Hoelscher, Adelia Castano, Jocelyn Parker, John Hoskins, Nicholas Anderson, Joseph Googe, Tod A. McMillan, James Miller, Stephen Perkins, Kristina Oliver, Jennifer Beerbower, Bruce Gilliland, Cecile Hunt, Mike Jacobus, Raul Lince, Christopher Morris, Sarah Oelrich, Jerry Whetstone, Clement K. Chan, Steven Lin, Kim Walther, Tiana Gonzales, Lenise Myers, Kenneth Huff, David M. Brown, Eric Chen, Matthew S. Benz, Richard H. Fish, Rosa Y. Kim, James Major, Tien Pei Wong, Charles Wycoff, Cassandra Cone, Debbie Goates Gilaspia, Nubia Landaverde, Robert Smith, Deneva Zamora, Veronica Sneed, Melina Vela, Eric Kegley, Craig Greven, Shree Kurup, Charles Richards, Madison Slusher, Cara Everhart, Joan Fish, Mark Clark, David Miller, Marshall Tyler, J. Michael Jumper, Arthur D. Fu, Robert N. Johnson, Brandon Lujan, H. Richard McDonald, Rosa Rodriguez, Nina Ansari, Jeanifer Joaquin, Silvia Linares, Lizette Lopez, Jessica Sabio, Sean Grout, Chad Indermill, Yesmin Urias, Roberto Zimmerman, Linda Margulies, Sara J. Schmidt, Joy L. Meier, Sherry L. Hadley, William Rosenthal, Barbara Johnson, Lois Swafford, Richard Shields, R. Scott Varner, Richard Rosen, Ronald Gentile, Melissa Rivas, Katy W. Tai, Wanda Carrasquillo-Boyd, Robert Masini, Glenn Stoller, Ken Carnevale, Diane M. LaRosa, Barbara Burger, Tereza Conway, Carla Del Castillo, Julissa Diaz, Susan Jones, Nina Mondoc, Charlene Balfour, C.H. Vitha, Jennifer Lutz, Barbara McGinley, Fadi El Baba, Ann Marie Lavorna, Renee Jones, Jean Lewis, Ruth Tenzler, Mary Salvas-Mladek, Diane Van Kesteren, W. Copley McLean, W. Zachery Bridges, Cameron Stone, Denise Ammons, Mary Lamy, Andrea Menzel, Lea Doll Raymer, Barbara Campbell, Lisa Hawkins, Leslie Rickman, Lorraine Sherlin, Paula Price, Albert Sinyai, Ronald Kingsley, Reagan H. Bradford, Robert E. Leonard, Sonny Icks, Vanessa Bergman, Brittany Ross, Russ Burris, Amanda Butt, Rob Richmond, Alice Lyon, Manjot Gill, Lee Jampol, Rukhsana Mizra, Zuzanna Rozenbajgier, Jeremy Chapman, Lori Kaminski, Andrea Degillio, Evica Simjanoski, Jeffrey Heier, Hyung Cho, Tina Scheufele Cleary, Darin Goldman, Chirag Shah, Trexler Topping, Marissa Weber, Torsten Wiegand, Jeremy Schindelheim, Joy Bankert, Jennifer Stone, Alison Nowak, Sandy Chong, Lindsay Williams, Steven Bennett, Dennis Donovan, Margaret Graham, Cullen Jones, Anne Fung, Jan-Kristine Bayabo, Razelda Bosch, Esperanza Cruz, Ashley Emerson, Alycia Fleming, Denice Barsness, Jorge Rodriguez, Marina Soboleva, Ingrid U. Scott, Esther Bowie, Kimberly A. Neely, David A. Quillen, Laura Walter, Timothy Bennett, James Strong, John Wells, Lloyd Clark, David Johnson, Peggy Miller, Mallie Taylor, Tiffany Swinford, Robbin Spivey, Michael Banach, Lawrence Ho, Richard Lanning, Thomas R. Pheasant, Jay G. Prensky, Steven Truong, Julia Teatsworth, Michelle Dietrich, Ann Wasilus, Ann Miller, Megan Rakes, Teresa Slagle, Michelle Richards, Patricia Schuessler, Lacy Stover, Paul Beer, Naomi S. Falk, Mary Beth Shannon, Jeannie Olmeda, Don Berdeen, Joseph F. Fisher, James Folk, Stephen Russell, Barbara Taylor, Connie Hinz, Jean Walshire, Heather Stockman, Bruce Critser, Stefani Karakas, Cindy Montague, Randy Verdick, Omesh Gupta, Joseph Maguire, Christopher Brady, Francis Char DeCroos, Michael Dollin, Sunir Garg, Adam Gerstenblith, Julia Haller, Allen C. Ho, Jason Hsu, Richard Kaiser, John Pitcher, Carl Regillo, Rajiv Shah, Marc Spirn, William Tasman, James Vander, Noga Senderowitsch, Michele Formoso, Michelle Markun, Cedric George, Christina Centinaro, Lisa Grande, Stefanie Carey, Elaine Liebenbaum, SriniVas Sadda, Mark Humayun, Rachel Sierra, Elizabeth Corona, Margaret Padilla, Moonseok Nu, Sylvia Ramos, Cullen Barnett, Glenn Currie, Cornelia Gottlieb, Richard Garfinkel, Daniel Berinstein, Marcus Colyer, William Deegan, Michael Min-Shyue Lai, Robert Murphy, Michael Osman, Michael Rivers, Reginald Sanders, Manfred A. von Fricken, Debbie Oliver, Jeanne Kirshon, Tanya Alexander Snowden, Thomas Blondo, Alysia Cronise, Vanessa Denny, Kylie Mendez, Janine Newgen, Justin Davis, Mike Flory, Robert Frantz, Bryan Murphy, Steve Rauch, Judy E. Kim, Jane Bachman, Thomas B. Connor, Dennis P. Han, Kimberly Stepian, David V. Weinberg, William J. Wirostko, Krissa Packard, Tracy Kaczanowski, Vesper Williams, Vicki Barwick, Judy Flanders, Dennis Backes, Joe Beringer, Kristy Keller, Kathy Selchert, Paul Bernstein, Michael Teske, Albert Vitale, Susan Allman, Bonnie Carlstrom, Kimberley Wegner, Anne Haroldsen, Deborah Harrison, Cyrie Fry, James Gilman, Glen Jenkins, Paula Morris, Michael Rauser, Joseph Fan, Mukesh Suthar, Gisela Santiago, Kara Rollins Halsey, Christy Quesada, William Kiernan, Jesse Knabb, Richard Alan Lewis, Cindy Dorenbach, Steven Spencer, Dana Barnett, Joseph Morales, Barron C. Fishburne, Jeffrey G. Gross, Michael A. Magee, Amy Flowers, Angie McDowell, Randall Price, Suber Huang, Johnny Tang, Shawn Wilker, Cherie Hornsby, Lisa Ferguson, Kirk Krogstad, Riva Adamovsky, Peggy Allchin, Kathleen Carlton, Claudia Clow, Kelly Sholtis, Stephanie Burke, Mark Harrod, Stacie Hrvatin, Geoffrey Pankhurst, Nelson R. Sabates, Michael Cassell, Komal Desai, Abraham Poulose, Felix Sabates, Yin Chen, Gary Gallimore, Yolanda Konior, Nicola Kim, Sami Uwaydat, Deborah Troillett, Karen Aletter, Robert N. Frank, Gary Abrams, James Puklin, Asheesh Tewari, Cheryl Milanovic, Melanie Bailey, David Griffith, Dena McDonald, Kit Morehead, Zlatan Sadikovic, Lisa Schillace, Elizabeth Silvis, Brian Joondeph, Nancy Christmas, Alan Kimura, Mimi Liu, Stephen Petty, John Zilis, Jenny Benitez, Cassandra Berryman Catlett, Eric Fluegel, Shane Mowry, Hoang Nguyen, David Reflow, Odette M. Houghton, Seema Garg, Maurice B. Landers, Travis Meredith, Sandy Barnhart, Megha Karmalkar, Debra Cantrell, Rona Lyn Esquejo-Leon, Linda Manor, Sue Pope, David Stines, Amelia Stokely, Dean Hainsworth, Dyann Helming, Debbie Eichelberger, Mary Paige Leaton, Chuck Hamm, Edward Chaum, Alessandro Iannaccone, Barbara Jennings, Tracy Murray, Joe Mastellone, Robert Millay, Brian Kim, Theresa Goddard, Liza Jarrett Beaudette, Nina Changelian-Aitken, Fernando Corrada, Jason Dubuque, Raymond Iezzi, Sophie J. Bakri, Jose S. Pulido, Diane Vogen, Rebecca Nielsen, Karin Berg, Jean Burrington, Shannon Howard, Joan Overend, Zbigniew Krason, Denise Lewison, Thomas Link, Kevin J. Blinder, Nicholas E. Engelbrecht, M. Gilbert Grand, Daniel P. Joseph, Gaurav K. Shah, Bradley Smith, Matthew Thomas, Rhonda Weeks, Lynda Boyd, Dana Gabel, Ron Adelman, John Huang, James Kempton, Aaron Parnes, Jennifer Dupont, Elizabeth Perotti, Victoria Donaldson, Kenneth Fong, Pamela Ossorio, Anita Agarwal, Paul Sternberg, Sandy Owings, Tony Adkins, Elaine Lok, Garvin Munn, Buddy Skellie, Neelakshi Bhagat, Monique S. Roy, Marco Zarbin, Catherine Fay, Michael Lazar, Beth Malpica, Tatiana Mikheyav, Lawrence Ulanski, Jennifer Lim, Marcia Niec, Tametha Johnson, Yesenia Ovando, Catherine Nail Carroll, Mark Janowicz, Steven Schwartz, David Cupp, Michael Gorin, Gad Heilweil, Hamid Hosseini, Jean-Pierre Hubschman, Allan Kreiger, Tara Young McCannel, Carolyn Pan, David Sarraf, Irena Tsui, Joshua Udoetek, Vinad Voleti, Logan Hitchcock, Rosaleen Ostrick, Melissa Chun, Jennie Kageyama, Nilo Davila, Kristin Lipka, Christina Shin, Cynthia Owsley, Michael Albert, Richard Feist, John Mason, Martin Thomley, Angelia Johnson, Tracy Emond, Joanna Hamela, Angela Marsh, Karen Searcey, Kia Rookard, Yu-Guang He, Rafael L. Ufret-Vincenty, Mike Molai, William Anderson, John Horna, Alan Letson, Colleen Cebulla, Susie Chang, Fred Davidorf, Jill Salerno, Laura Sladoje, Christina Stetson, Jeri Perry, Scott Savage, Cynthia Toth, Glenn Jaffe, Stefanie Schuman, Neeru Sarin, Jim Crowell, Tiffanie Keaton, Michael Kelly, Brian Lutman, Marriner Skelly, Lauren Welch, Lawrence Morse, Allan Hunter, Susanna Soon-Chun Park, Cynthia Wallace, Ember Dhillon, Marisa Salvador, Barbara Holderreed, Karishma Chandra, Sashi Kaur, Ellen Redenbo, Smiley Hom, Michael Cooney, Irene Barbazetto, James M. Klancnik, John A. Sorenson, Lawrence Yannuzzi, Maria Scolaro, Eugene Agresta, Nancy Gonzalez, Sandeep Grover, K.V. Chalam, Shailesh Gupta, Christopher Lyons, Wenhua Li, Chirag Patel, Jose Carrion, Henry Ferreyra, Amberly Rodriguez, Iliana Molina, Gabriel Balea, Pam Emory, Marlene Rico, Giorgio Siqueiros, Alexander J. Brucker, Joshua Dunaief, Juan Grunwald, Benjamin Kim, Albert M. Maguire, Brian VanderBeek, Sheri Drossner, Joan DuPont, Rebecca Salvo, Jim Berger, Cheryl Devine, Bill Nyberg, Laurel Weeney, David DiLoreto, Mina Chung, Valerie Davis, Peter MacDowell, George O. Gara, Daniel Castillo, Andrea Czubinski, Melissa Keim, Brandi Hardy, Rachel Grunhaus Hollar, Lynn Schueckler, Alice T. Lyon, Aaron Weinberg, Mira Shiloach, Nicole Pelkofer, Qin Zhou, Laura McPoland, Rajendra Apte, P. Kumar Rao, Sam Pistorius, Jamie Kambarian, Eve Adcock, Sarah Gould, Melanie Quinn, Rhonda Curtis, Amy Frost, Charla Meyer, and Greg Rathert

Subjects
0303 health sciences, medicine.medical_specialty, Visual acuity, genetic structures, business.industry, Eye disease, Hazard ratio, Age-Related Eye Disease Study, Retrospective cohort study, Fundus (eye), Macular degeneration, medicine.disease, eye diseases, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, 030221 ophthalmology & optometry, medicine, sense organs, medicine.symptom, Prospective cohort study, business, 030304 developmental biology
Abstract

Purpose To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). Design Retrospective analysis of a prospective cohort study. Participants Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Methods Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan–Meier analyses and multivariable proportional hazard regressions were performed. Main Outcome Measures Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Results Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98–2.82; P Conclusions This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

Published
2019
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22. Progression of Geographic Atrophy in Age-related Macular Degeneration

Author

Tiarnan D. Keenan, Elvira Agrón, Amitha Domalpally, Traci E. Clemons, Freekje van Asten, Wai T. Wong, Ronald G. Danis, SriniVas Sadda, Philip J. Rosenfeld, Michael L. Klein, Rinki Ratnapriya, Anand Swaroop, Frederick L. Ferris, Emily Y. Chew, John Paul SanGiovanni, Traci Clemons, Anne Lindblad, Robert Lindblad, Nilay Shah, Robert Sperduto, Wendy McBee, Gary Gensler, Molly Harrington, Alice Henning, Katrina Jones, Kumar Thotapally, Diana Tull, Valerie Watson, Kayla Williams, Christina Gentry, Francine Kaufman, Chris Morrison, Elizabeth Saverino, Sherrie Schenning, Barbara Blodi, Ronald P. Danis, Matthew Davis, Kathy Glander, Gregory Guilfoil, Larry D. Hubbard, Kristine Johnson, Ronald Klein, Barbara Nardi, Michael Neider, Nancy Robinson, Eileen Rosensteel, Hugh Wabers, Grace Zhang, Alan J. Ruby, Antonio Capone, Bawa Dass, Kimberly Drenser, Bruce R. Garretson, Tarek S. Hassan, Michael Trese, George A. Williams, Jeremy Wolfe, Tina Bell, Mary Zajechowski, Dennis Bezaire, Fran McIver, Anthony Medina, Jackie Pagett, Stephanie Hatch Smith, Lynn Swartz, Tom Treuter, Andrew Antoszyk, Justin Brown, David J. Browning, Walter Holland, Angella Karow, Kelly Stalford, Angela Price, Sarah Ennis, Sherry Fredenberg, Jenna Herby, Uma Balasubramaniam, Loraine Clark, Donna McClain, Michael McOwen, Lynn Watson, Michael Klein, Steven T. Bailey, Thomas J. Hwang, Andreas Lauer, J. Timothy Stout, Patty McCollum, Milt Johnson, Patrick B. Rice, Ivana Kim, John Loewenstein, Joan Miller, Lucia Sobrin, Lucy Young, Jacqueline Sullivan, Patricia Houlihan, Linda Merry, Ann Marie Lane, Ursula Lord Bator, Claudia Evans, Sarah Brett, Charleen Callahan, Marcia Grillo, David Walsh, Kamella Lau Zimmerman, Gary Edd Fish, Rajiv Anand, Lori E. Coors, Dwain G. Fuller, Rand Spencer, Robert C. Wang, Karen Duignan, Sally Arceneaux, Hank Aguado, Nicholas Hesse, Michael Mackens, Brian Swan, Catherine Cukras, Monica Dalal, Naima Jacobs-El, Catherine Meyerle, Benjamin Nicholson, Henry Wiley, Katherine Hall Shimel, Angel Garced, Janice Oparah, Greg Short, Alana Temple, Babilonia Ayukawa, Guy Foster, Darryl Hayes, Dessie Koutsandreas, Roula Nashwinter, John Rowan, Michael Bono, Denise Cunningham, Marilois Palmer, Alicia Zetina, David H. Orth, Kourous Rezaei, Joseph Civantos, Sohail Hasan, Kirk Packo, Celeste Figliulo, Pam Stanberry, Tara Farmer, Kiersten Nelson, Shannya Townsend-Patrick, Philip Rosenfeld, Royce Chen, Rishi Doshi, Sander Dubovy, Brian T. Kim, Matthew Lowrance, Andrew Moshfeghi, Zayna Nahas, Gary Schienbaum, John Vishak, Christina Weng, Zohar Yehoshua, Belen Rodriguez, Jose Rebimbas, Jane Gleichauf, Mike Kicak, Jason Mena, Tim Odem, Elizabeth Sferza-Camp, Alicia Disgdiertt, Jim Oramas, Isabel Rams, Stephanie Thatcher, Susan B. Bressler, Neil M. Bressler, Daniel Finkelstein, Steven H. Sherman, Sharon Solomon, Howard S. Ying, Rita Denbow, Deborah Phillips, Elizabeth Radcliffe, Judy Belt, Dennis Cain, David Emmert, Mark Herring, Jacquelyn McDonald, G. Baker Hubbard, Chris S. Bergstrom, Blaine Cribbs, Andrew Hendrick, Brandon Johnson, Philip Laird, Sonia Mehta, Timothy Olsen, Justin Townsend, Jion Yan, Steven Yeh, Linda Curtis, Judy Brower, Hannah Yi, Jannah Rutter Dobbs, Debbie Jordan, Michael J. Elman, Robert A. Liss, JoAnn Starr, Jennifer Belz, Charlene Putzulo, Teresa Coffey, Ashley Davis, Pamela Singletary, Giorya Shabi Andreani, Theresa Cain, Daniel Ketner, Peter Sotirakos, Suresh Chandra, Barbara A. Blodi, Michael M. Altaweel, Justin L. Gottlieb, Michael Ip, T. Michael Nork, Thomas S. Stevens, Kathryn Burke, Shelly Olson, Kristine Dietzman, Barbara Soderling, Guy Somers, Angie Wealti, Denise Krolnik, John Peterson, Sandra Reed, Thomas Friberg, Andrew Eller, Denise Gallagher, Leanne Labriola, Melissa Pokrifka, Aron Gedansky, Natalie Anthony, Cassandra Grzybowski, Dawn Matthews, Sharon Murajda-Jumba, Jessica Toro, David G. Callanan, Wayne A. Solley, Patrick Williams, Sandy Lash, Bob Boleman, Chris Dock, Michel Shami, Brenda Arrington, Ashaki Meeks, Alan R. Margherio, Paul Raphaelian, Debra Markus, Justin Langdon, Elizabeth Truax, Sandy Lewis, Brad Terry, Amy Noffke, Kean Oh, Ramin Sarrafizadeh, Scott Sneed, Julie Hammersley, Serena Neal, Mary Doran, Nan Jones, Lisa Preston, Heather Jessick, Tanya Tracy Marsh, Michael Tolentino, Adam Berger, Richard Hamilton, David Misch, Suk Jin Moon, Dawn Sutherland, Vera Dilts, Sara Henderson, Esmeralda Medina, Donald Trueman, Laura Holm, Jason Strickland, Darmakusuma Ie, Jeffrey L. Lipkowitz, Kekul B. Shah, Susan Geraghty, Beverly Sannazzaro, Morgan Harper, Krista Bayer, Mary B. Lansing, Lauren B. Fox, Rebecca Lee, Jay B. Stallman, Michael Jacobson, Sean Koh, Scott Lampert, John Miller, Mark Rivellese, Atul Sharma, Robert A. Stoltz, Stephanie Vanderveldt, Leslie Marcus, Starr Hendricks, Ryan Hollman, Grethel Betanzos, Leslie Ellorin, Shelly Fulbright, Debbie McCormick, Paul A. Edwards, Julianne Hall, Mary Monk, Melanie Gutkowski, Melina Mazurek, Janet Murphy, Katherine Gusas, Crystal Moffett, David Burley, Nicole Chesney, Katie Kilgo, Brian Rusinek, Bradley Stern, Tracy Troszak, Rhonda Baker-Levingston, Carl W. Baker, Tracey Caldwell, Tammy Walker, Lynnette F. Lambert, Tracey Martin, Mary Jill Palmer, Tana Williams, Michael A. Novak, Joseph Coney, David G. Miller, Scott Pendergast, Lawrence Singerman, Nicholas Zakov, Hernando Zegarra, Kim DuBois, Susan Rath, Lori Revella, Tammy Brink, Kim Drury, Lisa Hogue, Mary Ilc, Connie Keller, Elizabeth McNamara, Vivian Tanner, Tamara Cunningham, John DuBois, Gregg Greanoff, Trina Nitzsche, Sheila Smith-Brewer, Ricky D. Isernhagen, John W. Kitchens, Thomas W. Stone, William J. Wood, Diana Holcomb, Virginia Therrien, Michelle Buck, Jeanne Van Arsdall, Edward Slade, Todd E. Schneiderman, David J. Spinak, Jackie Gaedke, Heather Davis Brown, Dan Helgren, Jenifer Garrison Pangelinan, Lawrence Halperin, Scott Anagnoste, Mandeep Dhalla, Krista Rosenberg, Barry Taney, W. Scott Thompson, Jaclyn Lopez, Monica Hamlin, Monica Lopez, Jamie Mariano, Evelyn Quinchia, Patricia Aramayo, Rita Veksler, Michael Lee, Richard Dreyer, Irvin Handelman, Colin Ma, Mark Peters, Stephen Hobbs, Amanda Milliron, Marcia Kopfer, Michele Connaughton, A. Christine Hoerner, R. Joseph Logan, Harry J. Wohlsein, David Boyer, Thomas G. Chu, Pouya Dayani, David Liao, Roger L. Novack, Firas M. Rahhal, Richard Roe, Homayoun Tabandeh, Janet Bayramyan, Tammy Gasparyan, Connie Hoang, Janet Kurokouchi, Tammy Eileen Lo, Richard Ngo, Mary Ann Nguyen, Michael Peyton, Charles Yoon, Julio Sierra, Adam Zamboni, Jeff Kessinger, Eric Protacio, Adam Smucker, Pamela Rath, Robert Bergren, Bernard Doft, Judy Liu, Karl Olsen, Lori Merlotti, Willia Ingram, Kellianne Marfisi, Kimberly Yeckel, Heather Schultz Carmelo, Amanda Fec, Keith McBroom, David Steinberg, Marc Levy, Jody Abrams, Melvin Chen, Waldemar Torres, Peggy Jelemensky, Mark Prybylski, Tara Raphael, Diana Appleby, Charlotte Rodman, Mark Sneath, Robert H. Rosa, Vanessa Hoelscher, Adelia Castano, Jocelyn Parker, John Hoskins, Nicholas Anderson, Joseph Googe, Tod A. McMillan, James Miller, Stephen Perkins, Kristina Oliver, Jennifer Beerbower, Bruce Gilliland, Cecile Hunt, Mike Jacobus, Raul Lince, Christopher Morris, Sarah Oelrich, Jerry Whetstone, Clement K. Chan, Steven Lin, Kim Walther, Tiana Gonzales, Lenise Myers, Kenneth Huff, David M. Brown, Eric Chen, Matthew S. Benz, Richard H. Fish, Rosa Y. Kim, James Major, Tien Pei Wong, Charles Wycoff, Cassandra Cone, Debbie Goates Gilaspia, Nubia Landaverde, Robert Smith, Deneva Zamora, Veronica Sneed, Melina Vela, Eric Kegley, Craig Greven, Shree Kurup, Charles Richards, Madison Slusher, Cara Everhart, Joan Fish, Mark Clark, David Miller, Marshall Tyler, J. Michael Jumper, Arthur D. Fu, Robert N. Johnson, Brandon Lujan, H. Richard McDonald, Rosa Rodriguez, Nina Ansari, Jeanifer Joaquin, Silvia Linares, Lizette Lopez, Jessica Sabio, Sean Grout, Chad Indermill, Yesmin Urias, Roberto Zimmerman, Linda Margulies, Sara J. Schmidt, Joy L. Meier, Sherry L. Hadley, William Rosenthal, Barbara Johnson, Lois Swafford, Richard Shields, R. Scott Varner, Richard Rosen, Ronald Gentile, Melissa Rivas, Katy W. Tai, Wanda Carrasquillo-Boyd, Robert Masini, Glenn Stoller, Ken Carnevale, Diane M. LaRosa, Barbara Burger, Tereza Conway, Carla Del Castillo, Julissa Diaz, Susan Jones, Nina Mondoc, Charlene Balfour, C.H. Vitha, Jennifer Lutz, Barbara McGinley, Fadi El Baba, Ann Marie Lavorna, Renee Jones, Jean Lewis, Ruth Tenzler, Mary Salvas-Mladek, Diane Van Kesteren, W. Copley McLean, W. Zachery Bridges, Cameron Stone, Denise Ammons, Mary Lamy, Andrea Menzel, Lea Doll Raymer, Barbara Campbell, Lisa Hawkins, Leslie Rickman, Lorraine Sherlin, Paula Price, Albert Sinyai, Ronald Kingsley, Reagan H. Bradford, Robert E. Leonard, Sonny Icks, Vanessa Bergman, Brittany Ross, Russ Burris, Amanda Butt, Rob Richmond, Alice Lyon, Manjot Gill, Lee Jampol, Rukhsana Mizra, Zuzanna Rozenbajgier, Jeremy Chapman, Lori Kaminski, Andrea Degillio, Evica Simjanoski, Jeffrey Heier, Hyung Cho, Tina Scheufele Cleary, Darin Goldman, Chirag Shah, Trexler Topping, Marissa Weber, Torsten Wiegand, Jeremy Schindelheim, Joy Bankert, Jennifer Stone, Alison Nowak, Sandy Chong, Lindsay Williams, Steven Bennett, Dennis Donovan, Margaret Graham, Cullen Jones, Anne Fung, Jan-Kristine Bayabo, Razelda Bosch, Esperanza Cruz, Ashley Emerson, Alycia Fleming, Denice Barsness, Jorge Rodriguez, Marina Soboleva, Ingrid U. Scott, Esther Bowie, Kimberly A. Neely, David A. Quillen, Laura Walter, Timothy Bennett, James Strong, John Wells, Lloyd Clark, David Johnson, Peggy Miller, Mallie Taylor, Tiffany Swinford, Robbin Spivey, Michael Banach, Lawrence Ho, Richard Lanning, Thomas R. Pheasant, Jay G. Prensky, Steven Truong, Julia Teatsworth, Michelle Dietrich, Ann Wasilus, Ann Miller, Megan Rakes, Teresa Slagle, Michelle Richards, Patricia Schuessler, Lacy Stover, Paul Beer, Naomi S. Falk, Mary Beth Shannon, Jeannie Olmeda, Don Berdeen, Joseph F. Fisher, James Folk, Stephen Russell, Barbara Taylor, Connie Hinz, Jean Walshire, Heather Stockman, Bruce Critser, Stefani Karakas, Cindy Montague, Randy Verdick, Omesh Gupta, Joseph Maguire, Christopher Brady, Francis Char DeCroos, Michael Dollin, Sunir Garg, Adam Gerstenblith, Julia Haller, Allen C. Ho, Jason Hsu, Richard Kaiser, John Pitcher, Carl Regillo, Rajiv Shah, Marc Spirn, William Tasman, James Vander, Noga Senderowitsch, Michele Formoso, Michelle Markun, Cedric George, Christina Centinaro, Lisa Grande, Stefanie Carey, Elaine Liebenbaum, Mark Humayun, Rachel Sierra, Elizabeth Corona, Margaret Padilla, Moonseok Nu, Sylvia Ramos, Cullen Barnett, Glenn Currie, Cornelia Gottlieb, Richard Garfinkel, Daniel Berinstein, Marcus Colyer, William Deegan, Michael Min-Shyue Lai, Robert Murphy, Michael Osman, Michael Rivers, Reginald Sanders, Manfred A. von Fricken, Debbie Oliver, Jeanne Kirshon, Tanya Alexander Snowden, Thomas Blondo, Alysia Cronise, Vanessa Denny, Kylie Mendez, Janine Newgen, Justin Davis, Mike Flory, Robert Frantz, Bryan Murphy, Steve Rauch, Judy E. Kim, Jane Bachman, Thomas B. Connor, Dennis P. Han, Kimberly Stepian, David V. Weinberg, William J. Wirostko, Krissa Packard, Tracy Kaczanowski, Vesper Williams, Vicki Barwick, Judy Flanders, Dennis Backes, Joe Beringer, Kristy Keller, Kathy Selchert, Paul Bernstein, Michael Teske, Albert Vitale, Susan Allman, Bonnie Carlstrom, Kimberley Wegner, Anne Haroldsen, Deborah Harrison, Cyrie Fry, James Gilman, Glen Jenkins, Paula Morris, Michael Rauser, Joseph Fan, Mukesh Suthar, Gisela Santiago, Kara Rollins Halsey, Christy Quesada, William Kiernan, Jesse Knabb, Richard Alan Lewis, Cindy Dorenbach, Steven Spencer, Dana Barnett, Joseph Morales, Barron C. Fishburne, Jeffrey G. Gross, Michael A. Magee, Amy Flowers, Angie McDowell, Randall Price, Suber Huang, Johnny Tang, Shawn Wilker, Cherie Hornsby, Lisa Ferguson, Kirk Krogstad, Riva Adamovsky, Peggy Allchin, Kathleen Carlton, Claudia Clow, Kelly Sholtis, Stephanie Burke, Mark Harrod, Stacie Hrvatin, Geoffrey Pankhurst, Nelson R. Sabates, Michael Cassell, Komal Desai, Abraham Poulose, Felix Sabates, Yin Chen, Gary Gallimore, Yolanda Konior, Nicola Kim, Sami Uwaydat, Deborah Troillett, Karen Aletter, Robert N. Frank, Gary Abrams, James Puklin, Asheesh Tewari, Cheryl Milanovic, Melanie Bailey, David Griffith, Dena McDonald, Kit Morehead, Zlatan Sadikovic, Lisa Schillace, Elizabeth Silvis, Brian Joondeph, Nancy Christmas, Alan Kimura, Mimi Liu, Stephen Petty, John Zilis, Jenny Benitez, Cassandra Berryman Catlett, Eric Fluegel, Shane Mowry, Hoang Nguyen, David Reflow, Odette M. Houghton, Seema Garg, Maurice B. Landers, Travis Meredith, Sandy Barnhart, Megha Karmalkar, Debra Cantrell, Rona Lyn Esquejo-Leon, Linda Manor, Sue Pope, David Stines, Amelia Stokely, Dean Hainsworth, Dyann Helming, Debbie Eichelberger, Mary Paige Leaton, Chuck Hamm, Edward Chaum, Alessandro Iannaccone, Barbara Jennings, Tracy Murray, Joe Mastellone, Robert Millay, Brian Kim, Theresa Goddard, Liza Jarrett Beaudette, Nina Changelian-Aitken, Fernando Corrada, Jason Dubuque, Raymond Iezzi, Sophie J. Bakri, Jose S. Pulido, Diane Vogen, Rebecca Nielsen, Karin Berg, Jean Burrington, Shannon Howard, Joan Overend, Zbigniew Krason, Denise Lewison, Thomas Link, Kevin J. Blinder, Nicholas E. Engelbrecht, M. Gilbert Grand, Daniel P. Joseph, Gaurav K. Shah, Bradley Smith, Matthew Thomas, Rhonda Weeks, Lynda Boyd, Dana Gabel, Ron Adelman, John Huang, James Kempton, Aaron Parnes, Jennifer Dupont, Elizabeth Perotti, Victoria Donaldson, Kenneth Fong, Pamela Ossorio, Anita Agarwal, Paul Sternberg, Sandy Owings, Tony Adkins, Elaine Lok, Garvin Munn, Buddy Skellie, Neelakshi Bhagat, Monique S. Roy, Marco Zarbin, Catherine Fay, Michael Lazar, Beth Malpica, Tatiana Mikheyav, Lawrence Ulanski, Jennifer Lim, Marcia Niec, Tametha Johnson, Yesenia Ovando, Catherine Nail Carroll, Mark Janowicz, Steven Schwartz, David Cupp, Michael Gorin, Gad Heilweil, Hamid Hosseini, Jean-Pierre Hubschman, Allan Kreiger, Tara Young McCannel, Carolyn Pan, David Sarraf, Irena Tsui, Joshua Udoetek, Vinad Voleti, Logan Hitchcock, Rosaleen Ostrick, Melissa Chun, Jennie Kageyama, Nilo Davila, Kristin Lipka, Christina Shin, Cynthia Owsley, Michael Albert, Richard Feist, John Mason, Martin Thomley, Angelia Johnson, Tracy Emond, Joanna Hamela, Angela Marsh, Karen Searcey, Kia Rookard, Yu-Guang He, Rafael L. Ufret-Vincenty, Mike Molai, William Anderson, John Horna, Alan Letson, Colleen Cebulla, Susie Chang, Fred Davidorf, Jill Salerno, Laura Sladoje, Christina Stetson, Jeri Perry, Scott Savage, Cynthia Toth, Glenn Jaffe, Stefanie Schuman, Neeru Sarin, Jim Crowell, Tiffanie Keaton, Michael Kelly, Brian Lutman, Marriner Skelly, Lauren Welch, Lawrence Morse, Allan Hunter, Susanna Soon-Chun Park, Cynthia Wallace, Ember Dhillon, Marisa Salvador, Barbara Holderreed, Karishma Chandra, Sashi Kaur, Ellen Redenbo, Smiley Hom, Michael Cooney, Irene Barbazetto, James M. Klancnik, John A. Sorenson, Lawrence Yannuzzi, Maria Scolaro, Eugene Agresta, Nancy Gonzalez, Sandeep Grover, K.V. Chalam, Shailesh Gupta, Christopher Lyons, Wenhua Li, Chirag Patel, Jose Carrion, Henry Ferreyra, Amberly Rodriguez, Iliana Molina, Gabriel Balea, Pam Emory, Marlene Rico, Giorgio Siqueiros, Alexander J. Brucker, Joshua Dunaief, Juan Grunwald, Benjamin Kim, Albert M. Maguire, Brian VanderBeek, Sheri Drossner, Joan DuPont, Rebecca Salvo, Jim Berger, Cheryl Devine, Bill Nyberg, Laurel Weeney, David DiLoreto, Mina Chung, Valerie Davis, Peter MacDowell, George O. Gara, Daniel Castillo, Andrea Czubinski, Melissa Keim, Brandi Hardy, Rachel Grunhaus Hollar, Lynn Schueckler, Alice T. Lyon, Aaron Weinberg, Mira Shiloach, Nicole Pelkofer, Qin Zhou, Laura McPoland, Rajendra Apte, P. Kumar Rao, Sam Pistorius, Jamie Kambarian, Eve Adcock, Sarah Gould, Melanie Quinn, Rhonda Curtis, Amy Frost, Charla Meyer, and Greg Rathert

Subjects
0301 basic medicine, medicine.medical_specialty, genetic structures, business.industry, Eye disease, Incidence (epidemiology), Fundus (eye), Macular degeneration, medicine.disease, eye diseases, Confidence interval, Geographic atrophy, 03 medical and health sciences, Ophthalmology, 030104 developmental biology, 0302 clinical medicine, Age related, 030221 ophthalmology & optometry, medicine, sense organs, Prospective cohort study, business
Abstract

Purpose To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement. Design Prospective cohort study within a controlled clinical trial. Participants Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50–85 years. Methods Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype. Main Outcome Measures (1) Presence or development of GA; (2) change in the square root of GA area over time. Results At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27–0.30) and incident GA (0.28 mm/year; 0.27–0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P Conclusions Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

Published
2018
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24. Three-Dimensional Analysis of Vocal Fold Oscillations: Correlating Superior and Medial Surface Dynamics Using Ex Vivo Human Hemilarynges

Author

Reinhard Veltrup, Susanne Angerer, Elena Gessner, Friederike Matheis, Emily Sümmerer, Jann-Ole Henningson, Michael Döllinger, and Marion Semmler

Subjects
hemilarynx, 3D laryngoscopy, high-speed imaging, laryngeal modeling, mucosal wave propagation, empirical eigenfunctions, Technology, Biology (General), QH301-705.5
Abstract

The primary acoustic signal of the voice is generated by the complex oscillation of the vocal folds (VFs), whereby physicians can barely examine the medial VF surface due to its anatomical inaccessibility. In this study, we investigated possibilities to infer medial surface dynamics by analyzing correlations in the oscillatory behavior of the superior and medial VF surfaces of four human hemilarynges, each in 24 different combinations of flow rate, VF adduction, and elongation. The two surfaces were recorded synchronously during sustained phonation using two high-speed camera setups and were subsequently 3D-reconstructed. The 3D surface parameters of mean and maximum velocities and displacements and general phonation parameters were calculated. The VF oscillations were also analyzed using empirical eigenfunctions (EEFs) and mucosal wave propagation, calculated from medial surface trajectories. Strong linear correlations were found between the 3D parameters of the superior and medial VF surfaces, ranging from 0.8 to 0.95. The linear regressions showed similar values for the maximum velocities at all hemilarynges (0.69–0.9), indicating the most promising parameter for predicting the medial surface. Since excessive VF velocities are suspected to cause phono-trauma and VF polyps, this parameter could provide added value to laryngeal diagnostics in the future.

Published
2024
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25. Computational fluid dynamics of upper airway aerodynamics for exercise‐induced laryngeal obstruction: A feasibility study

Author

Michael Döllinger, Bernhard Jakubaß, Hu Cheng, Stephen J. Carter, Stefan Kniesburges, Bea Aidoo, Chi Hwan Lee, Claudio Milstein, and Rita R. Patel

Subjects
computational fluid dynamics (CFD), exercise‐induced laryngeal obstruction (EILO), paradoxical vocal fold motion, speech therapy, voice therapy, Otorhinolaryngology, RF1-547, Surgery, RD1-811
Abstract

Abstract Objective Use of computational fluid dynamic (CFD) simulations to measure the changes in upper airway geometry and aerodynamics during (a) an episode of Exercise‐Induced Laryngeal Obstruction (EILO) and (b) speech therapy exercises commonly employed for patients with EILO. Methods Magnetic resonance imaging stills of the upper airway including the nasal and oral cavities from an adult female were used to re‐construct three‐dimensional geometries of the upper airway. The CFD simulations were used to compute the maximum volume flow rate (l/s), pressure (Pa), airflow velocity (m/s) and area of cross‐section opening in eight planes along the vocal tract, separately for inhalation and exhalation. Results Numerical predictions from three‐dimensional geometrical modeling of the upper airway suggest that the technique of nose breathing for inhalation and pursed lip breathing for exhalation show most promising pressure conditions and cross‐sectional diameters for rescue breathing exercises. Also, if EILO is due to the constriction at the vocal fold level, then a quick sniff may also be a proper rescue inhalation exercise. EILO affects both the inspiratory and the expiratory phases of breathing. Conclusions A prior knowledge of the supraglottal aerodynamics and the corresponding upper airway geometry from CFD analysis has the potential to assist the clinician in choosing the most effective rescue breathing technique for optimal functional outcome of speech therapy intervention in patients with EILO and in understanding the pathophysiology of EILO on a case‐by‐case basis with future studies. Level of Evidence 4

Published
2023
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26. Machine Learning-assisted immunophenotyping of peripheral blood identifies innate immune cells as best predictor of response to induction chemo-immunotherapy in head and neck squamous cell carcinoma – knowledge obtained from the CheckRad-CD8 trial

Author

Markus Hecht, Benjamin Frey, Udo S. Gaipl, Xie Tianyu, Markus Eckstein, Anna-Jasmina Donaubauer, Gunther Klautke, Thomas Illmer, Maximilian Fleischmann, Simon Laban, Matthias G. Hautmann, Bálint Tamaskovics, Thomas B. Brunner, Ina Becker, Jian-Guo Zhou, Arndt Hartmann, Rainer Fietkau, Heinrich Iro, Michael Döllinger, Antoniu-Oreste Gostian, and Andreas M. Kist

Subjects
Chemotherapy, Immunotherapy, HNSCC, Induction therapy, Immune phenotyping, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Purpose: Individual prediction of treatment response is crucial for personalized treatment in multimodal approaches against head-and-neck squamous cell carcinoma (HNSCC). So far, no reliable predictive parameters for treatment schemes containing immunotherapy have been identified. This study aims to predict treatment response to induction chemo-immunotherapy based on the peripheral blood immune status in patients with locally advanced HNSCC. Methods: The peripheral blood immune phenotype was assessed in whole blood samples in patients treated in the phase II CheckRad-CD8 trial as part of the pre-planned translational research program. Blood samples were analyzed by multicolor flow cytometry before (T1) and after (T2) induction chemo-immunotherapy with cisplatin/docetaxel/durvalumab/tremelimumab. Machine Learning techniques were used to predict pathological complete response (pCR) after induction therapy. Results: The tested classifier methods (LDA, SVM, LR, RF, DT, and XGBoost) allowed a distinct prediction of pCR. Highest accuracy was achieved with a low number of features represented as principal components. Immune parameters obtained from the absolute difference (lT2-T1l) allowed the best prediction of pCR. In general, less than 30 parameters and at most 10 principal components were needed for highly accurate predictions. Across several datasets, cells of the innate immune system such as polymorphonuclear cells, monocytes, and plasmacytoid dendritic cells are most prominent. Conclusions: Our analyses imply that alterations of the innate immune cell distribution in the peripheral blood following induction chemo-immuno-therapy is highly predictive for pCR in HNSCC.

Published
2024
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27. Endogenous methicillin-resistant Staphylococcus aureus endophthalmitis secondary to axillary phlegmon: a case report

Author

Sunir J. Garg, Ehsan Rahimy, Michael Dollin, and Vinay Kansal

Subjects
business.industry, General Medicine, medicine.disease, medicine.disease_cause, Methicillin-resistant Staphylococcus aureus, Microbiology, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, Endophthalmitis, Phlegmon, 030221 ophthalmology & optometry, medicine, 030212 general & internal medicine, business
Published
2017
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28. MICROBIAL SPECTRUM AND OUTCOMES OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION VERSUS PARS PLANA VITRECTOMY

Author

Jason Hsu, John D. Pitcher, Philip Storey, Michael Dollin, James F. Vander, Sunir J. Garg, and Natalie Hsiao Fang-Yen

Subjects
0301 basic medicine, Pars plana, medicine.medical_specialty, genetic structures, business.industry, medicine.medical_treatment, Infectious endophthalmitis, Vitrectomy, General Medicine, medicine.disease, eye diseases, Surgery, 03 medical and health sciences, Ophthalmology, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Endophthalmitis, 030221 ophthalmology & optometry, medicine, business
Abstract

Purpose:To compare infectious organisms and visual outcomes of endophthalmitis after intravitreal injection (IVI) with endophthalmitis after pars plana vitrectomy (PPV).Methods:Retrospective, comparative, consecutive case series of patients diagnosed with presumed infectious endophthalmitis after IV

Published
2016
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29. Validation and enhancement of a vocal fold medial surface 3D reconstruction approach for in-vivo application

Author

Patrick Schlegel, Michael Döllinger, Neha K. Reddy, Zhaoyan Zhang, and Dinesh K. Chhetri

Subjects
Medicine, Science
Abstract

Abstract In laryngeal research, studying the vertical vocal fold oscillation component is often disregarded. However, vocal fold oscillation by its nature is a three-dimensional process. In the past, we have developed an in-vivo experimental protocol to reconstruct the full, three-dimensional vocal fold vibration. The goal of this study is to validate this 3D reconstruction method. We present an in-vivo canine hemilarynx setup using high-speed video recording and a right-angle prism for 3D reconstruction of vocal fold medial surface vibrations. The 3D surface is reconstructed from the split image provided by the prism. For validation, reconstruction error was calculated for objects located at a distance of up to 15 mm away from the prism. The influence of camera angle, changing calibrated volume, and calibration errors were determined. Overall average 3D reconstruction error is low and does not exceed 0.12 mm at 5 mm distance from the prism. Influence of a moderate (5°) and large (10°) deviation in camera angle led to a slight increase in error to 0.16 mm and 0.17 mm, respectively. This procedure is robust towards changes in calibration volume and small calibration errors. This makes this 3D reconstruction approach a useful tool for the reconstruction of accessible and moving tissue surfaces.

Published
2023
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30. Effect of a Strict ‘No-Talking’ Policy During Intravitreal Injection on Post-Injection Endophthalmitis

Author

James F. Vander, Michael Dollin, Philip Storey, Sunir J. Garg, and Jason Hsu

Subjects
Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Bevacizumab, Recombinant Fusion Proteins, Angiogenesis Inhibitors, Post injection, Eye Infections, Bacterial, Postoperative Complications, Endophthalmitis, Risk Factors, Ranibizumab, Internal medicine, Humans, Speech, Medicine, Practice Patterns, Physicians', Aged, Retrospective Studies, Aged, 80 and over, Bacteria, business.industry, Incidence, Incidence (epidemiology), Mouth Mucosa, Retrospective cohort study, Consecutive case series, Middle Aged, medicine.disease, Organizational Policy, Anti-Bacterial Agents, Receptors, Vascular Endothelial Growth Factor, Intravitreal Injections, Usual care, Female, business, medicine.drug
Abstract

BACKGROUND AND OBJECTIVE: To report the effect of a “no-talking” policy during intravitreal injection (IVI) on post-injection endophthalmitis. PATIENTS AND METHODS: Retrospective, comparative, consecutive case series of patients receiving IVI between Jan. 1, 2009, and Dec. 31, 2012. A 24-month “usual care” period was compared to a 24-month no-talking period, during which a strategy to further minimize speech during IVI was implemented. RESULTS: During the usual care period, 47,155 IVIs were performed, with nine culture-positive cases (0.019%), including seven due to oral pathogens (0.015%). During the no-talking period, 82,658 IVIs were performed, with eight culture-positive cases (0.010%), including two due to oral pathogens (0.002%). The no-talking policy was associated with a decreased endophthalmitis risk ( P = .004), including oral pathogen-associated endophthalmitis ( P = .02). CONCLUSION: This study demonstrates that a more stringent no-talking policy during IVI may reduce the risk of post-injection endophthalmitis. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:1028–1034.]

Published
2015
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31. Contemporary Management of Rhegmatogenous Retinal Detachment Due to Giant Retinal Tears: A Consecutive Case Series

Author

Philip Storey, Carl D. Regillo, Jason Hsu, Allen C. Ho, Michael Dollin, John D. Pitcher, Natalie Hsiao-Fang-Yen, Sunir J. Garg, and Mohammed Ali Khan

Subjects
Adult, Male, Pars plana, medicine.medical_specialty, Visual acuity, Adolescent, genetic structures, medicine.medical_treatment, Sulfur Hexafluoride, Visual Acuity, Vitrectomy, Endotamponade, Vitreoretinal Surgery, Scleral buckle, chemistry.chemical_compound, Ophthalmology, medicine, Humans, Silicone Oils, Aged, Retrospective Studies, Aged, 80 and over, Fluorocarbons, business.industry, Retinal Detachment, Retinal detachment, Retinal, Consecutive case series, Middle Aged, Retinal Perforations, medicine.disease, Retinal Tear, Scleral Buckling, medicine.anatomical_structure, chemistry, Female, medicine.symptom, business
Abstract

BACKGROUND AND OBJECTIVE: To investigate outcomes of contemporary surgical techniques for repair of rhegmatogenous retinal detachments (RRD) associated with giant retinal tears (GRT). PATIENTS AND METHODS: Retrospective, consecutive case series including 58 eyes of 58 patients. Mean age was 52 years (range: 16 to 83 years). All patients underwent 23-gauge pars plana vitrectomy with use of perfluorocarbon liquid and intravitreal tamponade (28 with silicone oil, 25 with octafluoropropane gas, and five with sulfur hexafluoride gas). Scleral buckle (SB) was placed in 30 eyes (52%). RESULTS: At a mean follow-up of 17 months, mean visual acuity improved from 20/500 preoperatively to 20/88 at final follow-up. Fifty-one patients (88%) had single-surgery anatomic success, and all patients achieved final retinal reattachment. Use of SB ( P = 1.0), silicone oil ( P = .1), or 360° endophotocoagulation ( P = .7) did not correlate with higher rates of successful repair. CONCLUSION: Contemporary vitreoretinal surgery techniques achieve high rates of primary anatomic success in GRT-related RRDs. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:566–570.]

Published
2015
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32. Neural network-based estimation of biomechanical vocal fold parameters

Author

Jonas Donhauser, Bogac Tur, and Michael Döllinger

Subjects
convolutional recurrent neural network, high-speed video, mass–spring–damper system, vocal fold dynamics, voice physiology, Physiology, QP1-981
Abstract

Vocal fold (VF) vibrations are the primary source of human phonation. High-speed video (HSV) endoscopy enables the computation of descriptive VF parameters for assessment of physiological properties of laryngeal dynamics, i.e., the vibration of the VFs. However, underlying biomechanical factors responsible for physiological and disordered VF vibrations cannot be accessed. In contrast, physically based numerical VF models reveal insights into the organ’s oscillations, which remain inaccessible through endoscopy. To estimate biomechanical properties, previous research has fitted subglottal pressure-driven mass–spring–damper systems, as inverse problem to the HSV-recorded VF trajectories, by global optimization of the numerical model. A neural network trained on the numerical model may be used as a substitute for computationally expensive optimization, yielding a fast evaluating surrogate of the biomechanical inverse problem. This paper proposes a convolutional recurrent neural network (CRNN)-based architecture trained on regression of a physiological-based biomechanical six-mass model (6 MM). To compare with previous research, the underlying biomechanical factor “subglottal pressure” prediction was tested against 288 HSV ex vivo porcine recordings. The contributions of this work are two-fold: first, the presented CRNN with the 6 MM handles multiple trajectories along the VFs, which allows for investigations on local changes in VF characteristics. Second, the network was trained to reproduce further important biomechanical model parameters like VF mass and stiffness on synthetic data. Unlike in a previous work, the network in this study is therefore an entire surrogate of the inverse problem, which allowed for explicit computation of the fitted model using our approach. The presented approach achieves a best-case mean absolute error (MAE) of 133 Pa (13.9%) in subglottal pressure prediction with 76.6% correlation on experimental data and a re-estimated fundamental frequency MAE of 15.9 Hz (9.9%). In-detail training analysis revealed subglottal pressure as the most learnable parameter. With the physiological-based model design and advances in fast parameter prediction, this work is a next step in biomechanical VF model fitting and the estimation of laryngeal kinematics.

Published
2024
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33. Vowel onset measures and their reliability, sensitivity and specificity: A systematic literature review.

Author

Antonia Margarita Chacon, Duy Duong Nguyen, John Holik, Michael Döllinger, Tomás Arias-Vergara, and Catherine Jeanette Madill

Subjects
Medicine, Science
Abstract

ObjectiveTo systematically evaluate the evidence for the reliability, sensitivity and specificity of existing measures of vowel-initial voice onset.MethodsA literature search was conducted across electronic databases for published studies (MEDLINE, EMBASE, Scopus, Web of Science, CINAHL, PubMed Central, IEEE Xplore) and grey literature (ProQuest for unpublished dissertations) measuring vowel onset. Eligibility criteria included research of any study design type or context focused on measuring human voice onset on an initial vowel. Two independent reviewers were involved at each stage of title and abstract screening, data extraction and analysis. Data extracted included measures used, their reliability, sensitivity and specificity. Risk of bias and certainty of evidence was assessed using GRADE as the data of interest was extracted.ResultsThe search retrieved 6,983 records. Titles and abstracts were screened against the inclusion criteria by two independent reviewers, with a third reviewer responsible for conflict resolution. Thirty-five papers were included in the review, which identified five categories of voice onset measurement: auditory perceptual, acoustic, aerodynamic, physiological and visual imaging. Reliability was explored in 14 papers with varied reliability ratings, while sensitivity was rarely assessed, and no assessment of specificity was conducted across any of the included records. Certainty of evidence ranged from very low to moderate with high variability in methodology and voice onset measures used.ConclusionsA range of vowel-initial voice onset measurements have been applied throughout the literature, however, there is a lack of evidence regarding their sensitivity, specificity and reliability in the detection and discrimination of voice onset types. Heterogeneity in study populations and methods used preclude conclusions on the most valid measures. There is a clear need for standardisation of research methodology, and for future studies to examine the practicality of these measures in research and clinical settings.

Published
2024
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34. OPACIFICATION OF SCLERAL-SUTURED AKREOS AO60 INTRAOCULAR LENS AFTER VITRECTOMY WITH GAS TAMPONADE: CASE SERIES

Author

Ananda Kalevar, R. Rishi Gupta, and Michael Dollin

Subjects
Pars plana, Male, medicine.medical_specialty, Visual acuity, genetic structures, medicine.medical_treatment, Visual Acuity, Vitrectomy, Intraocular lens, Endotamponade, Slit Lamp Microscopy, Aphakia, Ectopia Lentis, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Suture (anatomy), Lens Implantation, Intraocular, Ophthalmology, medicine, Humans, Ectopia lentis, Aged, Lenses, Intraocular, Sutures, business.industry, General Medicine, Middle Aged, medicine.disease, eye diseases, medicine.anatomical_structure, 030221 ophthalmology & optometry, sense organs, Tamponade, medicine.symptom, business, 030217 neurology & neurosurgery, Sclera
Abstract

BACKGROUND/PURPOSE We report the first two cases of postoperative opacification of scleral-sutured Akreos AO60 intraocular lens after vitrectomy with the gas tamponade. METHODS Two patients with ectopia lentis underwent pars plana vitrectomy, pars plana lensectomy, and scleral fixation of an Akreos AO60 intraocular lens with Gore-Tex suture. Retinal breaks were noted during vitrectomy and consequently intravitreal gas tamponade was used after endolaser retinopexy. Postoperatively, both patients developed intraocular lens opacification but maintained excellent visual acuity; however, one patient developed bothersome though tolerable photophobia. CONCLUSION Although still an excellent option for the management of surgical aphakia in the absence of capsular support, caution should be taken when using a hydrophilic secondary intraocular lens, such as Akreos AO60, during vitreoretinal surgery if gas is required.

Published
2017

36. Ocular involvement in sarcoidosis

Author

Vinay Kansal and Michael Dollin

Subjects
Adult, medicine.medical_specialty, Activities of daily living, genetic structures, Photophobia, Eye Diseases, Sarcoidosis, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, 0502 economics and business, medicine, Humans, Ocular pain, Practice, business.industry, 05 social sciences, General Medicine, medicine.disease, Dermatology, eye diseases, 030221 ophthalmology & optometry, 050211 marketing, Female, sense organs, medicine.symptom, business
Abstract

A 27-year-old woman presented to her family doctor with bilateral ocular pain that waxed and waned, redness and photophobia. The symptoms had progressed over several months and were followed by hoarseness and dyspnea, all of which interfered with her activities of daily living. The patient’s

Published
2017

37. Acute and Painless Monocular Vision Loss in a Human Immunodeficiency Virus-Positive Man

Author

Vinay Kansal and Michael Dollin

Subjects
Adult, Male, medicine.medical_specialty, Human Immunodeficiency Virus Positive, Trunk structure, Eye pain, Blindness, Eye Infections, Bacterial, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Vision, Monocular, HIV Seropositivity, medicine, Eye Pain, Humans, Syphilis, Fluorescein Angiography, Homosexuality, Male, Glucocorticoids, Monocular, business.industry, Penicillin G, Eye infection, medicine.disease, Dermatology, Immunologic Deficiency Syndromes, Surgery, Anti-Bacterial Agents, Ophthalmology, Chorioretinitis, Acute Disease, 030221 ophthalmology & optometry, business, Monocular vision, 030217 neurology & neurosurgery, Tomography, Optical Coherence
Published
2017

38. Scleral Fixation of Posterior Chamber Intraocular Lenses Using Gore-Tex Suture With Concurrent 23-Gauge Pars Plana Vitrectomy

Author

Mohammed Ali Khan, Michael Dollin, Marc J. Spirn, Adam T. Gerstenblith, and Omesh P. Gupta

Subjects
Male, Pars plana, medicine.medical_specialty, medicine.medical_treatment, Visual Acuity, Vitrectomy, Lens Implantation, Intraocular, Ophthalmology, medicine, Humans, Polytetrafluoroethylene, Aged, Lenses, Intraocular, Fibrous joint, Sutures, business.industry, Suture Techniques, General Medicine, Scleral fixation, medicine.anatomical_structure, Intraocular lenses, Female, business, Sclera
Published
2014
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39. Pars Plana Lensectomy After Femtosecond Laser-Assisted Cataract Surgery

Author

Sunir J. Garg, Sagun Pendse, and Michael Dollin

Subjects
Reoperation, medicine.medical_specialty, genetic structures, medicine.medical_treatment, Visual Acuity, Cataract Extraction, Vitrectomy, Ophthalmology, Humans, Medicine, Intraoperative Complications, Aged, business.industry, Lens Cortex, Crystalline, Cataract surgery, Laser assisted, eye diseases, medicine.anatomical_structure, Posterior capsule, Lens (anatomy), Pars plana lensectomy, Femtosecond, Female, Laser Therapy, sense organs, business
Abstract

The use of femtosecond laser during cataract surgery is increasing, as it may potentially improve accuracy, safety and refractive outcomes. However, posterior capsule rupture with retained lens material can occur, necessitating vitreoretinal intervention. The authors report the first videographically documented case of removal of retained lens material after femtosecond laser-assisted cataract surgery. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:680–682.]

Published
2015
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40. GlottisNetV2: Temporal Glottal Midline Detection Using Deep Convolutional Neural Networks

Author

Elina Kruse, Michael Dollinger, Anne Schutzenberger, and Andreas M. Kist

Subjects
Laryngeal endoscopy, glottis, deep neural networks, deep learning, midline, biomedical imaging, Computer applications to medicine. Medical informatics, R858-859.7, Medical technology, R855-855.5
Abstract

High-speed videoendoscopy is a major tool for quantitative laryngology. Glottis segmentation and glottal midline detection are crucial for computing vocal fold-specific, quantitative parameters. However, fully automated solutions show limited clinical applicability. Especially unbiased glottal midline detection remains a challenging problem. We developed a multitask deep neural network for glottis segmentation and glottal midline detection. We used techniques from pose estimation to estimate the anterior and posterior points in endoscopy images. Neural networks were set up in TensorFlow/Keras and trained and evaluated with the BAGLS dataset. We found that a dual decoder deep neural network termed GlottisNetV2 outperforms the previously proposed GlottisNet in terms of MAPE on the test dataset (1.85% to 6.3%) while converging faster. Using various hyperparameter tunings, we allow fast and directed training. Using temporal variant data on an additional data set designed for this task, we can improve the median prediction accuracy from 2.1% to 1.76% when using 12 consecutive frames and additional temporal filtering. We found that temporal glottal midline detection using a dual decoder architecture together with keypoint estimation allows accurate midline prediction. We show that our proposed architecture allows stable and reliable glottal midline predictions ready for clinical use and analysis of symmetry measures.

Published
2023
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41. 25-GAUGE TROCAR CANNULA FOR ACUTE ENDOPHTHALMITIS-RELATED IN-OFFICE VITREOUS TAP AND INJECTION: Patient Comfort and Physician Ease of Use

Author

Michael Dollin, Murtaza K. Adam, Joseph I. Maguire, and Sina Vahedi

Subjects
Pars plana, Male, medicine.medical_specialty, Catheters, genetic structures, Attitude of Health Personnel, Pilot Projects, 03 medical and health sciences, 0302 clinical medicine, Endophthalmitis, Port (medical), medicine, Humans, Sampling (medicine), Prospective Studies, Patient Comfort, Patient comfort, Aged, Aged, 80 and over, business.industry, Biopsy, Needle, General Medicine, Pain scale, Middle Aged, medicine.disease, Cannula, eye diseases, Surgery, Vitreous Body, Ophthalmology, Acute endophthalmitis, medicine.anatomical_structure, Anesthesia, Intravitreal Injections, 030221 ophthalmology & optometry, Female, sense organs, business, 030217 neurology & neurosurgery
Abstract

To assess comfort and procedural facility using a 25-gauge trocar cannula as a port to diagnose and treat acute endophthalmitis compared with a standard vitreous tap and injection technique. Eighteen consecutive patients with acute endophthalmitis were randomized into two treatment arms: 1) Standard vitreous tap and injection technique, and 2) A technique where a valved 25-gauge trocar cannula is inserted through the pars plana as done in sutureless vitrectomy surgery and subsequent vitreous sampling and injections are performed through the port. A standardized anesthetic protocol was used and subjects were masked to the technique performed. Primary outcomes measured were patient comfort using a Wong-Baker pain scale and standardized physician ease-of-use scoring scale. Secondary outcomes included vitreous sampling success rate and volume of vitreous sample. No significant differences were found when comparing patient comfort (P = 0.340), physician ease-of-use scores (P = 0.796), vitreous sample volume (P = 0.149), successful vitreous taps (P = 0.620), and microbiologic yield (P = 1.000) between treatment arms. There were no adverse events. The 25-gauge trocar technique provides a safe, well-tolerated, and equally effective alternative to the standard vitreous tap and injection technique for delivery of intravitreal antibiotics, and procuring of vitreous sample, requiring a single sharp penetration.

Published
2016

42. Adult-onset exposure keratitis after childhood ptosis repair with frontalis sling procedure

Author

James H. Oestreicher and Michael Dollin

Subjects
Adult, Male, medicine.medical_specialty, Lagophthalmos, Facial Muscles, Ophthalmologic Surgical Procedures, Keratitis, Young Adult, Postoperative Complications, Ptosis, medicine, Blepharoptosis, Humans, Strabismus, Retrospective Studies, Unilateral ptosis, business.industry, General Medicine, Middle Aged, medicine.disease, Surgery, Entropion, Ophthalmology, medicine.anatomical_structure, Oculomotor Muscles, Female, Eyelid, Ophthalmic Solutions, medicine.symptom, business, Strabismus surgery
Abstract

Objective: To report the development of adult-onset exposure keratitis in patients having undergone childhood ptosis repair with frontalis sling surgery (FSS). Study Design: Retrospective, noncomparative case series. Participants: Seven patients having received childhood FSS who were referred to us as adults with a complaint of ocular dryness that did not develop until years after surgery. Methods: Single-centre, clinic-based, chart review. Results: Four patients had bilateral, congenital ptosis and 3 had unilateral ptosis, secondary to childhood trauma (2) and third nerve palsy (1). Mean age at first FSS was 6 years (range, 9 months-14 years). Five patients had received additional ophthalmic surgery, including strabismus surgery (2), repeat FSS (4), and prior failed levator resection (1). Mean age at referral to our centre with complaint of ocular dryness was 37 years (range, 23–46 years). Mean time from most recent FSS to presentation was 23 years (range, 17–36 years). On examination, 6 patients had related eyelid abnormalities, including bilateral entropion (1), ptosis recurrence (4), and peaked upper eyelid (1). All patients had measurable lagophthalmos (range, 0.5 mm-3 mm), and 5 had detectable punctate keratopathy (range, "trace" to "2+" on a scale of 0 to 4+). All patients were offered artificial lubricating drops, and 3 were deemed candidates for corrective eyelid surgery, resulting in improvement of exposure keratitis. Conclusions: Adult-onset exposure keratitis should be included as a potential late complication of FSS ptosis repair in children, particularly when multiple surgeries are required or complications occur.

Published
2009
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43. Rapid additive-free TEMPO-mediated stable free radical polymerizations of styrene

Author

Michael K. Georges, Michael Dollin, and Andrea R. Szkurhan

Subjects
Polymers and Plastics, Bulk polymerization, Chemistry, Camphorsulfonic acid, Organic Chemistry, Dispersity, Radical polymerization, Benzoyl peroxide, Photochemistry, Styrene, chemistry.chemical_compound, Acetic anhydride, Polymerization, Polymer chemistry, Materials Chemistry, medicine, medicine.drug
Abstract

The stable free radical polymerization (SFRP) of styrene, initiated with benzoyl peroxide in the presence of TEMPO, under bulk conditions, is demonstrated to proceed rapidly without the need for any rate enhancing additives such as camphorsulfonic acid, 2-fluoro-1-methyl pyridinium p-toluenesulfonate, or acetic anhydride. Monomer conversions as high as 70% can be achieved in 5 h or less while maintaining polydispersity indexes of 1.15. These results stand in stark contrast to earlier reactions that required 70 h to achieve similar conversions. This study demonstrates that the single largest factor governing the rates of polymerization is the molar concentration of excess TEMPO remaining in solution after initiation. A reduction in the TEMPO to BPO ratio is required when large amounts of BPO are used to target low molecular weight polystyrenes. However, when a lower molar amount of BPO is used to obtain high molecular weight polystyrenes, a higher TEMPO to BPO ratio is required. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5487–5493, 2007

Published
2007
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44. Trends in subspecialty training by Canadian ophthalmology graduates

Author

Nirojini Sivachandran, Michael Dollin, Michael D. O’Connor, Jason Noble, and R. Rishi Gupta

Subjects
Male, medicine.medical_specialty, Canada, Cross-sectional study, education, 030209 endocrinology & metabolism, Subspecialty, 03 medical and health sciences, 0302 clinical medicine, Ophthalmology, Surveys and Questionnaires, medicine, Humans, Oculoplastics, Career decision, Fellowships and Scholarships, health care economics and organizations, Career Choice, business.industry, Internship and Residency, General Medicine, Test (assessment), Cross-Sectional Studies, Education, Medical, Graduate, Family medicine, 030221 ophthalmology & optometry, Workforce planning, Pediatric ophthalmology, Female, business, Postgraduate training, Specialization
Abstract

Objective To evaluate the trends in subspecialty fellowship training by Canadian ophthalmology graduates over the last 25 years. Design Cross-sectional study. Participants Canadian-funded, Royal College–certified graduates from 1990 to 2014 who completed a full residency in an English-language Canadian ophthalmology postgraduate training program. Methods Data were obtained by contacting all 11 English-language ophthalmology residency programs across Canada for demographic and fellowship information regarding their graduates. Society web sites were then used to corroborate and complement the data set, including those of the Canadian Ophthalmology Society, American Academy of Ophthalmology, and Provincial Colleges of Physicians and Surgeons. Data were organized by demographic variables, and analysis was performed using SPSS v22.0. Results Of the 528 graduates from 1990 to 2014, 63.5% pursued fellowship training. Males and females were equally likely to undertake fellowship training. The proportion of graduates obtaining fellowship training did not change significantly during this 25-year period. The most popular subspecialty choices were vitreoretinal surgery (24.5%), glaucoma (16.7%), and anterior segment (16.7%). Significantly more males than females pursued vitreoretinal surgery and oculoplastics fellowships ( p = 0.001, χ 2 test), whereas females were more likely to train in a paediatric ophthalmology and strabismus fellowship ( p = 0.001, χ 2 test). Conclusions The majority of ophthalmology graduates from English-language residency programs pursue subspecialty fellowship training. An understanding of trends in fellowship training may be helpful for both workforce planning and career decision making.

Published
2015

45. Endophthalmitis

Author

Michael Dollin and Jason Hsu

Subjects
medicine.medical_specialty, Endophthalmitis, business.industry, Ophthalmology, Medicine, business, medicine.disease
Published
2015
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47. The effect of prophylactic topical antibiotics on bacterial resistance patterns in endophthalmitis following intravitreal injection

Author

John D. Pitcher, Nadim Rayess, Michael Dollin, James F. Vander, Sunir J. Garg, Sahitya Reddy, Jason Hsu, and Philip Storey

Subjects
0301 basic medicine, Vascular Endothelial Growth Factor A, medicine.medical_specialty, medicine.drug_class, VEGF receptors, Administration, Topical, Antibiotics, Topical antibiotics, Visual Acuity, Angiogenesis Inhibitors, Eye Infections, Bacterial, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Antibiotic resistance, Endophthalmitis, Internal medicine, Drug Resistance, Bacterial, medicine, Humans, Retrospective Studies, biology, Bacteria, business.industry, Antibiotic Prophylaxis, medicine.disease, Sensory Systems, Surgery, Anti-Bacterial Agents, Ophthalmology, Drug Combinations, 030104 developmental biology, Case-Control Studies, Intravitreal Injections, 030221 ophthalmology & optometry, biology.protein, Ophthalmic Solutions, business
Abstract

The purpose of this study was to evaluate the effect of prophylactic topical antibiotics on bacterial resistance patterns in endophthalmitis following intravitreal injection of anti-vascular endothelial growth factor (VEGF) medications.In this retrospective case-control study, billing records and an infection log were used to identify all cases of endophthalmitis following intravitreal injection of ranibizumab, bevacizumab, or aflibercept between January 1, 2009 and September 30, 2013 at a single retina practice. A 28-month period when topical antibiotic drops were prescribed for use four times a day for 4 days following intravitreal injection was compared to a 21-month period when topical antibiotics were not prescribed. Patients treated during an 8-month transition period were excluded as prescription practices were changed.During the study period, a total of 172,096 anti-VEGF injections were performed. During the period when antibiotics were prescribed, 28 cases of suspected infectious endophthalmitis occurred from a total of 57,654 injections, ten of which were culture-positive. During the period when antibiotics were not used, 24 cases of suspected endophthalmitis occurred from a total of 89,825 injections, six of which were culture-positive. During the antibiotic period, four of the ten (40 %) culture-positive cases grew bacteria resistant to the prescribed prophylactic antibiotics. In contrast, none of the six culture-positive cases grew bacteria resistant to those antibiotics during the period when antibiotics were not used (odds ratio = 9.0; 95 % confidence interval = 0.40-203.3; p = 0.17).The use of prophylactic topical antibiotics following intravitreal injection may lead to higher rates of antibiotic-resistant bacteria in culture-positive endophthalmitis cases.

Published
2014

48. The role of topical antibiotic prophylaxis to prevent endophthalmitis after intravitreal injection

Author

Philip Storey, James F. Vander, Sahitya Reddy, Joseph Vojtko, John D. Pitcher, Sunir J. Garg, Michael Dollin, and Jason Hsu

Subjects
Male, medicine.medical_specialty, medicine.drug_class, Administration, Topical, Antibiotics, Visual Acuity, Angiogenesis Inhibitors, Ceftazidime, Eye Infections, Bacterial, Endophthalmitis, Retinal Diseases, Vancomycin, Medicine, Humans, Antibiotic prophylaxis, Amikacin, Aflibercept, Aged, Retrospective Studies, Bacteria, business.industry, Incidence (epidemiology), Incidence, Eye infection, Antibiotic Prophylaxis, Middle Aged, medicine.disease, Surgery, Anti-Bacterial Agents, Vitreous Body, Ophthalmology, Anesthesia, Case-Control Studies, Chemoprophylaxis, Intravitreal Injections, Female, Ranibizumab, Ophthalmic Solutions, business, medicine.drug
Abstract

Objective To compare the incidence of endophthalmitis after intravitreal injection with and without topical postinjection antibiotic prophylaxis. Design Retrospective case-control study. Participants All patients treated with intravitreal injection of ranibizumab, bevacizumab, or aflibercept for a variety of retinal vascular diseases at a single, large retina practice between January 1, 2009, and October 1, 2012, were included. Methods The total numbers of patients and injections were determined from a review of billing code and practice management records. Endophthalmitis cases were determined from billing records and from an infection log. All cases of endophthalmitis were confirmed with chart review. A 28-month period when topical antibiotics were prescribed after intravitreal injection was compared with a 9-month period when topical antibiotics were not prescribed. Patients treated during an 8-month transition period were excluded to allow for the conversion of antibiotic prescription practices. Main Outcome Measures Incidence of endophthalmitis, visual acuity outcomes, and microbial spectrum. Results During the study period, a total of 117 171 intravitreal injections were performed (57 654 injections during the topical antibiotic period, 24 617 during the transition period, and 34 900 during the no-antibiotic period), with a total of 44 cases of suspected endophthalmitis (0.038%; 1 in 2663 injections), 17 of which showed culture-positive results (0.015%; 1 in 6892 injections). During the 28-month topical antibiotic period, there were 28 cases of suspected endophthalmitis (0.049%; 1 in 2059 injections), 10 of which showed culture-positive results (0.017%; 1 in 5765 injections). During the 9-month no-antibiotic period, there were 11 cases of suspected endophthalmitis (0.032%; 1 in 3173 injections), 4 of which showed culture-positive results (0.011%; 1 in 8725 injections). Topical antibiotic use was associated with a trend toward increased risk of suspected endophthalmitis (odds ratio [OR], 1.54; 95% confidence interval [CI], 0.77–3.10) and culture-positive endophthalmitis (OR, 1.51; 95% CI, 0.47–4.83). Conclusions The incidence of endophthalmitis after intravitreal injection is low. Using postinjection topical antibiotic drops does not reduce the risk of endophthalmitis developing and is associated with a trend toward higher incidence of endophthalmitis.

Published
2013

49. OpenHSV: an open platform for laryngeal high-speed videoendoscopy

Author

Andreas M. Kist, Stephan Dürr, Anne Schützenberger, and Michael Döllinger

Subjects
Medicine, Science
Abstract

Abstract High-speed videoendoscopy is an important tool to study laryngeal dynamics, to quantify vocal fold oscillations, to diagnose voice impairments at laryngeal level and to monitor treatment progress. However, there is a significant lack of an open source, expandable research tool that features latest hardware and data analysis. In this work, we propose an open research platform termed OpenHSV that is based on state-of-the-art, commercially available equipment and features a fully automatic data analysis pipeline. A publicly available, user-friendly graphical user interface implemented in Python is used to interface the hardware. Video and audio data are recorded in synchrony and are subsequently fully automatically analyzed. Video segmentation of the glottal area is performed using efficient deep neural networks to derive glottal area waveform and glottal midline. Established quantitative, clinically relevant video and audio parameters were implemented and computed. In a preliminary clinical study, we recorded video and audio data from 28 healthy subjects. Analyzing these data in terms of image quality and derived quantitative parameters, we show the applicability, performance and usefulness of OpenHSV. Therefore, OpenHSV provides a valid, standardized access to high-speed videoendoscopy data acquisition and analysis for voice scientists, highlighting its use as a valuable research tool in understanding voice physiology. We envision that OpenHSV serves as basis for the next generation of clinical HSV systems.

Published
2021
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