Bio


Dr. Chang is a fellowship-trained refractive cataract and glaucoma specialist working at Stanford since 2009 and Co-Director of the Stanford Glaucoma Fellowship. He focuses on premium lenses (Panoptix and Vivity) as well as minimally invasive glaucoma surgery (i.e. Hydrus, OMNI, iTrack, ECP, KDB, iStent, Xen, MP3). He has performed thousands of cases and trained many fellows across the country. His funded clinical research and data science team harnesses glaucoma insights from the Stanford Glaucoma Registry of Real World Evidence combining longitudinal electronic records, imaging, and a growing biorepository of aqueous samples. Previously, he helped develop the normative databases for the ubiquitous optical coherence tomography (OCT) and is an expert in testing novel portable medical devices (i.e. virtual reality headsets), enabling home monitoring (Xala Health), and validating algorithms. He is formally trained in biodesign, biopharma, process improvement science, and leadership training.

Dr. Chang co-invented the EyeGo Smartphone imaging adapter, which was licensed and commercialized as the Paxos Scope. He previously co-founded a venture-backed seed stage consumer health startup and is a scientific advisor board member to multiple Fortune 500 and small pharmaceutical, med device, and digital health companies. He has served as Vice President of the Asia Pacific Tele Ophthalmology Society and Medical Director of employer based optometry services and regularly speaks on glaucoma and digital technology at conferences around the world. One of his original contributions is the creation of the digital health design sprint, a week-long, fully immersive, project-based learning experience to help doctors, engineers, and business experts be more aware of the challenges in starting a healthcare company.

Clinical Focus


  • Glaucoma and cataract surgery
  • Minimally Invasive Surgical Procedures
  • Mobile Health
  • Optical Coherence Tomography
  • Myopia
  • Vision Screening
  • eye
  • ECP
  • hydrus
  • design thinking
  • Entrepreneurship
  • Glaucoma Specialist

Academic Appointments


  • Associate Professor - University Medical Line, Ophthalmology
  • Member, Bio-X

Administrative Appointments


  • Medical Director, Stanford Employer Based Optometry (2016 - Present)
  • Glaucoma Fellowship Co-Director, Stanford Ophthalmology (2009 - Present)

Honors & Awards


  • Heed Fellow, Heed Foundation (2007)
  • America Glaucoma Society MAPS grant, AGS (2011)
  • Bio-X Undergraduate Summer Research Program Grant, Stanford (2013)
  • Winner Best Pivot, Stanford Startxmed Innovation Challenge (2013)
  • Stanford Center Peking University Faculty Fellowship Program Award, SCPKU (2014)
  • Stanford Society of Physician Scholars (SSPS) Grant, SSPS (2014)
  • Stanford Spectrum Medtech Innovation Grant, Spectrum (2014)
  • Circular 2D Polarized LCD TV on Improvement of Eye Fatigue and Eye Movement Control, TCL Research America Grant (2014-2015)
  • First Place, Philips Healthsuite Hackathon (2015)
  • Stanford Center Peking University Graduate Seminar Program, SCPKU (2015)
  • Digital Health Bootcamp, SCPKU (2016)
  • Medical Innovation Curriculum, Stanford UAR (2016)
  • Robert Howard Next Step Award, Lunar (2016)
  • Stanford Spectrum Medtech Innovation Grant, Spectrum (2016)
  • Center for Innovation in Global Health Grant, CIGH Stanford (2017)
  • Machine Learning Grant, Santen (2017)
  • Biorepository Grant, Genentech (2021)

Boards, Advisory Committees, Professional Organizations


  • Fellow, AAO American Academy of Ophthalmology (2009 - Present)
  • Member, AGS American Glaucoma Society (2009 - Present)
  • Fellow, CIGH Center for Innovation in Global Health (2015 - Present)
  • Vice President, APTOS Asia Pacific Tele-Ophthalmology Society (2016 - 2021)
  • Member and Co-Chair mHealth, PHS Population Health Sciences (2015 - 2016)

Professional Education


  • Internship: McGaw Medical Center of Northwestern University (2004) IL
  • Fellowship: Bascom Palmer Eye Institute (2009) FL
  • Residency: Washington University Ophthalmology Residency (2007) MO
  • Medical Education: University of Missouri Kansas City School of Medicine Registrar (2002) MO
  • Board Certification: American Board of Ophthalmology, Ophthalmology (2008)

Patents


  • Robert Chang. "United States Patent 62/138,271 Modular Smartphone Adapters for Mobile Ophthalmoscopy", Leland Stanford Junior University, Mar 25, 2015
  • Robert Chang. "United States Patent 14/893,951 Modular Lens Adapters for Mobile Anterior and Posterior Segment Ophthalmoscopy,", Leland Stanford Junior University, May 30, 2014

Research Interests


  • Data Sciences
  • Technology and Education

Current Research and Scholarly Interests


I am a clinician-scientist focusing on patient care, physician innovation and biodesign educator, and digital health technology.

Selected Interests:
1) Young High Myopes with Minimally Progressive Field Defects
2) Visual Field and Optical Coherence Tomography Specificity for Progression in Glaucoma
3) Patient Satisfaction in Ophthalmology
4) Automated Visual Field Screening for Glaucoma Using Portable Headsets
5) Automated Image Analysis and Natural Language Processing, Federated Learning
6) Smartphone-Based Tele-Ophthalmology Screening For Eye Disease

2023-24 Courses


Stanford Advisees


All Publications


  • Developing a privacy-preserving deep learning model for glaucoma detection: a multicentre study with federated learning. The British journal of ophthalmology Ran, A. R., Wang, X., Chan, P. P., Wong, M. O., Yuen, H., Lam, N. M., Chan, N. C., Yip, W. W., Young, A. L., Yung, H. W., Chang, R. T., Mannil, S. S., Tham, Y. C., Cheng, C. Y., Wong, T. Y., Pang, C. P., Heng, P. A., Tham, C. C., Cheung, C. Y. 2023

    Abstract

    Deep learning (DL) is promising to detect glaucoma. However, patients' privacy and data security are major concerns when pooling all data for model development. We developed a privacy-preserving DL model using the federated learning (FL) paradigm to detect glaucoma from optical coherence tomography (OCT) images.This is a multicentre study. The FL paradigm consisted of a 'central server' and seven eye centres in Hong Kong, the USA and Singapore. Each centre first trained a model locally with its own OCT optic disc volumetric dataset and then uploaded its model parameters to the central server. The central server used FedProx algorithm to aggregate all centres' model parameters. Subsequently, the aggregated parameters are redistributed to each centre for its local model optimisation. We experimented with three three-dimensional (3D) networks to evaluate the stabilities of the FL paradigm. Lastly, we tested the FL model on two prospectively collected unseen datasets.We used 9326 volumetric OCT scans from 2785 subjects. The FL model performed consistently well with different networks in 7 centres (accuracies 78.3%-98.5%, 75.9%-97.0%, and 78.3%-97.5%, respectively) and stably in the 2 unseen datasets (accuracies 84.8%-87.7%, 81.3%-84.8%, and 86.0%-87.8%, respectively). The FL model achieved non-inferior performance in classifying glaucoma compared with the traditional model and significantly outperformed the individual models.The 3D FL model could leverage all the datasets and achieve generalisable performance, without data exchange across centres. This study demonstrated an OCT-based FL paradigm for glaucoma identification with ensured patient privacy and data security, charting another course toward the real-world transition of artificial intelligence in ophthalmology.

    View details for DOI 10.1136/bjo-2023-324188

    View details for PubMedID 37857452

  • Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo. Cell Wolf, J., Rasmussen, D. K., Sun, Y. J., Vu, J. T., Wang, E., Espinosa, C., Bigini, F., Chang, R. T., Montague, A. A., Tang, P. H., Mruthyunjaya, P., Aghaeepour, N., Dufour, A., Bassuk, A. G., Mahajan, V. B. 2023

    Abstract

    Single-cell analysis in living humans is essential for understanding disease mechanisms, but it is impractical in non-regenerative organs, such as the eye and brain, because tissue biopsies would cause serious damage. We resolve this problem by integrating proteomics of liquid biopsies with single-cell transcriptomics from all known ocular cell types to trace the cellular origin of 5,953 proteins detected in the aqueous humor. We identified hundreds of cell-specific protein markers, including for individual retinal cell types. Surprisingly, our results reveal that retinal degeneration occurs in Parkinson's disease, and the cells driving diabetic retinopathy switch with disease stage. Finally, we developed artificial intelligence (AI) models to assess individual cellular aging and found that many eye diseases not associated with chronological age undergo accelerated molecular aging of disease-specific cell types. Our approach, which can be applied to other organ systems, has the potential to transform molecular diagnostics and prognostics while uncovering new cellular disease and aging mechanisms.

    View details for DOI 10.1016/j.cell.2023.09.012

    View details for PubMedID 37863056

  • Biobanking of Human Aqueous and Vitreous Liquid Biopsies for Molecular Analyses. Journal of visualized experiments : JoVE Wolf, J., Chemudupati, T., Kumar, A., Rasmussen, D. K., Wai, K. M., Chang, R. T., Montague, A. A., Tang, P. H., Bassuk, A. G., Dufour, A., Mruthrunjaya, P., Mahajan, V. B. 2023

    Abstract

    A critical challenge in translational research is establishing a viable and efficient interface between patient care in the operating room (OR) and the research laboratory. Here, we developed a protocol for acquiring high-quality liquid biopsies for molecular analyses from the aqueous humor and the vitreous from patients undergoing eye surgery. In this workflow, a Mobile Operating Room Lab Interface (MORLI) cart equipped with a computer, a barcode scanner, and lab instruments, including onboard cold storage, is used to obtain and archive human biological samples. A web-based data privacy-compliant database enables annotating each sample over its lifetime, and a cartesian coordinate system allows tracking each barcoded specimen in storage, enabling quick and accurate retrieval of samples for downstream analyses. Molecular characterization of human tissue samples not only serves as a diagnostic tool (e.g., to distinguish between infectious endophthalmitis and other non-infectious intraocular inflammation) but also represents an important component of translational research, allowing the identification of new drug targets, development of new diagnostic tools, and personalized therapeutics.

    View details for DOI 10.3791/65804

    View details for PubMedID 37747194

  • Comparison of Ophthalmologist and Large Language Model Chatbot Responses to Online Patient Eye Care Questions. JAMA network open Bernstein, I. A., Zhang, Y. V., Govil, D., Majid, I., Chang, R. T., Sun, Y., Shue, A., Chou, J. C., Schehlein, E., Christopher, K. L., Groth, S. L., Ludwig, C., Wang, S. Y. 2023; 6 (8): e2330320

    Abstract

    Importance: Large language models (LLMs) like ChatGPT appear capable of performing a variety of tasks, including answering patient eye care questions, but have not yet been evaluated in direct comparison with ophthalmologists. It remains unclear whether LLM-generated advice is accurate, appropriate, and safe for eye patients.Objective: To evaluate the quality of ophthalmology advice generated by an LLM chatbot in comparison with ophthalmologist-written advice.Design, Setting, and Participants: This cross-sectional study used deidentified data from an online medical forum, in which patient questions received responses written by American Academy of Ophthalmology (AAO)-affiliated ophthalmologists. A masked panel of 8 board-certified ophthalmologists were asked to distinguish between answers generated by the ChatGPT chatbot and human answers. Posts were dated between 2007 and 2016; data were accessed January 2023 and analysis was performed between March and May 2023.Main Outcomes and Measures: Identification of chatbot and human answers on a 4-point scale (likely or definitely artificial intelligence [AI] vs likely or definitely human) and evaluation of responses for presence of incorrect information, alignment with perceived consensus in the medical community, likelihood to cause harm, and extent of harm.Results: A total of 200 pairs of user questions and answers by AAO-affiliated ophthalmologists were evaluated. The mean (SD) accuracy for distinguishing between AI and human responses was 61.3% (9.7%). Of 800 evaluations of chatbot-written answers, 168 answers (21.0%) were marked as human-written, while 517 of 800 human-written answers (64.6%) were marked as AI-written. Compared with human answers, chatbot answers were more frequently rated as probably or definitely written by AI (prevalence ratio [PR], 1.72; 95% CI, 1.52-1.93). The likelihood of chatbot answers containing incorrect or inappropriate material was comparable with human answers (PR, 0.92; 95% CI, 0.77-1.10), and did not differ from human answers in terms of likelihood of harm (PR, 0.84; 95% CI, 0.67-1.07) nor extent of harm (PR, 0.99; 95% CI, 0.80-1.22).Conclusions and Relevance: In this cross-sectional study of human-written and AI-generated responses to 200 eye care questions from an online advice forum, a chatbot appeared capable of responding to long user-written eye health posts and largely generated appropriate responses that did not differ significantly from ophthalmologist-written responses in terms of incorrect information, likelihood of harm, extent of harm, or deviation from ophthalmologist community standards. Additional research is needed to assess patient attitudes toward LLM-augmented ophthalmologists vs fully autonomous AI content generation, to evaluate clarity and acceptability of LLM-generated answers from the patient perspective, to test the performance of LLMs in a greater variety of clinical contexts, and to determine an optimal manner of utilizing LLMs that is ethical and minimizes harm.

    View details for DOI 10.1001/jamanetworkopen.2023.30320

    View details for PubMedID 37606922

  • Real-world agreement of same-visit Tono-Pen vs Goldmann applanation intraocular pressure measurements using electronic health records. Heliyon Gui, H., Zhang, Y., Chang, R. T., Wang, S. Y. 2023; 9 (8): e18703

    Abstract

    Purpose: To compare intraocular pressure (IOP) obtained with Tono-Pen (TP) and Goldmann applanation (GAT) using large-scale electronic health records (EHR).Design: Retrospective cohort study.Methods: A single pair of eligible TP/GAT IOP readings was randomly selected from the EHR for each ophthalmology patient at an academic ophthalmology center (2013-2022), yielding 4550 eligible measurements. We used Bland-Altman analysis to describe agreement between TP/GAT IOP differences and mean IOP measurements. We also used multivariable logistic regression to identify factors associated with different IOP readings in the same eye, including demographics, glaucoma diagnosis, and central corneal thickness (CCT). Primary outcome metrics were discrepant measurements between TP and GAT as defined by two methods: Outcome A (normal TP despite elevated GAT measurements), and Outcome B (TP and GAT IOP differences ≥6mmHg).Result: The mean TP/GAT IOP difference was 0.15mmHg (±5.49mmHg 95% CI). There was high correlation between the measurements (r=0.790, p<0.001). We found that TP overestimated pressures at IOP <16.5mmHg and underestimated at IOP >16.5mmHg (Fig. 4). Discrepant measurements accounted for 2.6% (N=116) and 5.2% (N=238) for outcomes A and B respectively. Patients with thinner CCT had higher odds of discrepant IOP (OR 0.88 per 25mum increase, CI [0.84-0.92], p<0.0001; OR 0.88 per 25mum increase, CI [0.84-0.92], p<0.0001 for outcomes A and B respectively).Conclusion: In a real-world academic practice setting, TP and GAT IOP measurements demonstrated close agreement, although 2.6% of measurements showed elevated GAT IOP despite normal TP measurements, and 5.2% of measurements were ≥6mmHg apart.

    View details for DOI 10.1016/j.heliyon.2023.e18703

    View details for PubMedID 37576221

  • Patterns and determinants of incident cataract surgery in China from 2011 to 2015 using a nationally representative longitudinal database. BMJ open Jan, C., Xin, J., Dong, Y., Butt, T., Chang, R., Keay, L., He, M., Friedman, D., Congdon, N. 2023; 13 (6): e069702

    Abstract

    OBJECTIVES: To investigate incident cataract surgery and to investigate determinants of cataract surgery uptake in Chinese adults.DESIGN: This nationally representative longitudinal study recorded self-reported incident cataract surgery, and measured biological, clinical and socioeconomical characteristics at baseline and endline.SETTING: In the first stage, 150 county-level units were randomly chosen with a probability-proportional-to-size sampling technique from a sampling frame containing all county-level units. The sample was stratified by region and within region by urban district or rural county and per capita gross domestic product. The final sample of 150 counties fell within 28 provinces of China.PARTICIPANTS: Urban and rural Chinese persons aged 45 years and older.PRIMARY AND SECONDARY OUTCOME MEASURES: Incident cataract surgery (primary outcome) and the factors associated with incident cataract surgery (secondary outcome).RESULTS: Among 16663 people enrolled in 2011, 13705 (82.2%) attended follow-up in 2015. Among these, 167 (1.22%) reported incident cataract surgery. Those receiving surgery were significantly older (66.2±8.79 vs 58.3±9.18, p≤0.001) and more likely to report: illiteracy (44.9% vs 27.1%, p<0.001), poor baseline distance vision (49.7% vs 20.0%, p≤0.001), poor baseline near vision (37.1% vs 21.8%, p≤0.001), baseline visual impairment (15.6% vs 5.5%, p≤0.001), diabetes (12.0% vs 7.42%, p≤0.05) and higher baseline depression scores (9.7 vs 8.4 on a scale of 0-30, p≤0.05). In linear regression models, older age, worse distance vision, hypertension or diabetes, illiteracy and lower depression score were significantly associated with undergoing surgery. Results were similar in models including only persons aged ≥60 years, except that urban residence was also associated with surgery. When only those aged ≥60 years with poor vision were included, results were again the same, except that higher household expenditure was also associated with surgery.CONCLUSIONS: In China, cataract surgical rates remain low; underserved groups such as rural dwellers are less likely to receive cataract surgery.

    View details for DOI 10.1136/bmjopen-2022-069702

    View details for PubMedID 37344116

  • Real-World Agreement of Same-Visit Tono-Pen Versus Goldmann Applanation Intraocular Pressure Measurements Using Electronic Health Records at an Academic Medical Center Zhang, Y., Gui, H., Chang, R., Wang, S. Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023
  • Glaucoma and Myopia: Diagnostic Challenges. Biomolecules Sun, M. T., Tran, M., Singh, K., Chang, R., Wang, H., Sun, Y. 2023; 13 (3)

    Abstract

    The rising global prevalence of myopia is a growing concern for clinicians, as it predisposes patients to severe ocular pathologies including glaucoma. High myopia can be associated with clinical features that resemble glaucomatous damage, which make an accurate glaucoma diagnosis challenging, particularly among patients with normal intraocular pressures. These patients may also present with established visual field defects which can mimic glaucoma, and standard imaging technology is less useful in disease detection and monitoring due to the lack of normative data for these anatomically unique eyes. Progression over time remains the most critical factor in facilitating the detection of early glaucomatous changes, and thus careful longitudinal follow-up of high-risk myopic patients is the most important aspect of management. Here, we review our current understanding of the complex relationship between myopia and glaucoma, and the diagnostic challenges and limitations of current testing protocols including visual field, intraocular pressure, and imaging. Furthermore, we discuss the clinical findings of two highly myopic patients with suspected glaucoma.

    View details for DOI 10.3390/biom13030562

    View details for PubMedID 36979497

  • Using deep leaning models to detect ophthalmic diseases: A comparative study. Frontiers in medicine Li, Z., Guo, X., Zhang, J., Liu, X., Chang, R., He, M. 2023; 10: 1115032

    Abstract

    Purpose: The aim of this study was to prospectively quantify the level of agreement among the deep learning system, non-physician graders, and general ophthalmologists with different levels of clinical experience in detecting referable diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy.Methods: Deep learning systems for diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy classification, with accuracy proven through internal and external validation, were established using 210,473 fundus photographs. Five trained non-physician graders and 47 general ophthalmologists from China were chosen randomly and included in the analysis. A test set of 300 fundus photographs were randomly identified from an independent dataset of 42,388 gradable images. The grading outcomes of five retinal and five glaucoma specialists were used as the reference standard that was considered achieved when ≥50% of gradings were consistent among the included specialists. The area under receiver operator characteristic curve of different groups in relation to the reference standard was used to compare agreement for referable diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy.Results: The test set included 45 images (15.0%) with referable diabetic retinopathy, 46 (15.3%) with age-related macular degeneration, 46 (15.3%) with glaucomatous optic neuropathy, and 163 (55.4%) without these diseases. The area under receiver operator characteristic curve for non-physician graders, ophthalmologists with 3-5years of clinical practice, ophthalmologists with 5-10years of clinical practice, ophthalmologists with >10years of clinical practice, and the deep learning system for referable diabetic retinopathy were 0.984, 0.964, 0.965, 0.954, and 0.990 (p=0.415), respectively. The results for referable age-related macular degeneration were 0.912, 0.933, 0.946, 0.958, and 0.945, respectively, (p=0.145), and 0.675, 0.862, 0.894, 0.976, and 0.994 for referable glaucomatous optic neuropathy, respectively (p<0.001).Conclusion: The findings of this study suggest that the accuracy of this deep learning system is comparable to that of trained non-physician graders and general ophthalmologists for referable diabetic retinopathy and age-related macular degeneration, but the deep learning system performance is better than that of trained non-physician graders for the detection of referable glaucomatous optic neuropathy.

    View details for DOI 10.3389/fmed.2023.1115032

    View details for PubMedID 36936225

  • Corrigendum to Phase 1b Randomized Controlled Study of Short Course Topical Recombinant Human Nerve Growth Factor (rhNGF) for Neuroenhancement in Glaucoma: Safety, Tolerability, and Efficacy Measure Outcomes. Am J Ophthalmol 2022;234:223-234. American journal of ophthalmology Beykin, G., Stell, L., Halim, M. S., Nunez, M., Popova, L., Nguyen, B. T., Groth, S. L., Dennis, A., Li, Z., Atkins, M., Khavari, T., Wang, S. Y., Chang, R., Fisher, A. C., Sepah, Y. J., Goldberg, J. L. 2022

    View details for DOI 10.1016/j.ajo.2022.07.018

    View details for PubMedID 35977854

  • Three-Dimensional Multi-Task Deep Learning Model to Detect Glaucomatous Optic Neuropathy and Myopic Features From Optical Coherence Tomography Scans: A Retrospective Multi-Centre Study. Frontiers in medicine Ran, A. R., Wang, X., Chan, P. P., Chan, N. C., Yip, W., Young, A. L., Wong, M. O., Yung, H. W., Chang, R. T., Mannil, S. S., Tham, Y. C., Cheng, C. Y., Chen, H., Li, F., Zhang, X., Heng, P. A., Tham, C. C., Cheung, C. Y. 2022; 9: 860574

    Abstract

    We aim to develop a multi-task three-dimensional (3D) deep learning (DL) model to detect glaucomatous optic neuropathy (GON) and myopic features (MF) simultaneously from spectral-domain optical coherence tomography (SDOCT) volumetric scans.Each volumetric scan was labelled as GON according to the criteria of retinal nerve fibre layer (RNFL) thinning, with a structural defect that correlated in position with the visual field defect (i.e., reference standard). MF were graded by the SDOCT en face images, defined as presence of peripapillary atrophy (PPA), optic disc tilting, or fundus tessellation. The multi-task DL model was developed by ResNet with output of Yes/No GON and Yes/No MF. SDOCT scans were collected in a tertiary eye hospital (Hong Kong SAR, China) for training (80%), tuning (10%), and internal validation (10%). External testing was performed on five independent datasets from eye centres in Hong Kong, the United States, and Singapore, respectively. For GON detection, we compared the model to the average RNFL thickness measurement generated from the SDOCT device. To investigate whether MF can affect the model's performance on GON detection, we conducted subgroup analyses in groups stratified by Yes/No MF. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and accuracy were reported.A total of 8,151 SDOCT volumetric scans from 3,609 eyes were collected. For detecting GON, in the internal validation, the proposed 3D model had significantly higher AUROC (0.949 vs. 0.913, p < 0.001) than average RNFL thickness in discriminating GON from normal. In the external testing, the two approaches had comparable performance. In the subgroup analysis, the multi-task DL model performed significantly better in the group of "no MF" (0.883 vs. 0.965, p-value < 0.001) in one external testing dataset, but no significant difference in internal validation and other external testing datasets. The multi-task DL model's performance to detect MF was also generalizable in all datasets, with the AUROC values ranging from 0.855 to 0.896.The proposed multi-task 3D DL model demonstrated high generalizability in all the datasets and the presence of MF did not affect the accuracy of GON detection generally.

    View details for DOI 10.3389/fmed.2022.860574

    View details for PubMedID 35783623

    View details for PubMedCentralID PMC9240220

  • Structural and Metabolic Imaging after Short-term Use of the Balance Goggles System in Glaucoma Patients: A Pilot Study. Journal of glaucoma Sun, M. T., Beykin, G., Lee, W. S., Sun, Y., Chang, R., Nunez, M., Li, K. Z., Knasel, C., Rich, C., Goldberg, J. L. 2022

    Abstract

    Short-term use of the Balance Goggles System in glaucoma patients was not associated with observable changes in conventional OCT imaging but metabolic imaging using peripapillary flavoprotein fluorescence may represent a useful adjuctive investigation.To determine whether the intraocular pressure (IOP)-lowering effects of the Balance Goggles System (BGS) are accompanied by changes in retinal thickness measured by ocular coherence tomography, retinal vascular density measured by OCT-angiography, or novel peripapillary metabolic profiling using flavoprotein fluorescence (FPF) measured by a fundus camera.Prospective comparative case-series.8 eyes from 8 patients with open-angle glaucoma ranging from mild to severe.In this prospective, single-center, open-label, non-randomized, single-arm study patients received a baseline evaluation including retinal imaging, then one hour of negative pressure application through the BGS, followed by repeat retinal imaging. Participants then used the BGS at home for 1 month and underwent a repeat evaluation at the conclusion of the trial.Changes in nerve fiber layer thickness, OCTA vascular parameters and FPF scores.Mean baseline IOP was 18.0±3.1 mmHg and there was no significant change in IOP at follow-up. At 1 month compared to baseline, there was a statistically significant improvement in FPF optic nerve head rim scores (12.7±11.6 to 10.5±7.5; P=0.04). Additionally, there was there was a trend towards an increase in RNFL thickness after 1 month (69.5±14.2 to 72.0±13.7; P=0.1), but there were no statistically significant differences observable with any of the OCTA vascular parameters either at 1 hour or after 1 month.There were no significant changes observable using conventional OCT imaging following short-term use of the BGS, although metabolic imaging using FPF may be a useful potential biomarker to complement existing investigations. Additional studies are warranted to further investigate these changes.

    View details for DOI 10.1097/IJG.0000000000002066

    View details for PubMedID 35696700

  • Repeatability and correlation of a virtual reality perimeter with standard automated perimetry in glaucoma patients Chaudhry, A., Berneshawi, A., Liu, J., Shue, A., Chang, D., Kim, J., Chang, R. T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Feasibility of Glaucoma Home Self Testing Using a Virtual Reality Visual Field Test Combined with Home Tonometry Berneshawi, A., Shue, A., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Correlated Changes in Retinal Thickness and Visuomotor Function in Asymptomatic Hydroxychloroquine Toxicity Patients Leung, L., Hwang, B., Berneshawi, A., Goel, R., Tyson, T., Chang, R. T., Stone, L. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Federated Deep Learning for Classifying Glaucomatous Optic Neuropathy from Optical Coherence Tomography Volumetric Scans: A Privacy-preserving Multi-national Study Ran, A., Wang, X., Chan, P. P., Chan, N. C., Wong, O., Yung, H., Chang, R. T., Mannil, S. S., Tham, Y., Cheng, C., Heng, P., Tham, C. C., Cheung, C. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Management of Key Ocular Adverse Events in Patients Implanted with the Port Delivery System with Ranibizumab. Ophthalmology. Retina Awh, C. C., Barteselli, G., Makadia, S., Chang, R. T., Stewart, J. M., Wieland, M. R., Brassard, R., Callaway, N. F., Gune, S., Heatherton, P., Malhotra, V., Willis, J. R., Pieramici, D. J. 2022

    Abstract

    PURPOSE: To provide strategies for the management of key ocular adverse events (AEs) that may be encountered with the Port Delivery System with ranibizumab (PDS) in practice, and to provide recommendations that may mitigate such AEs based on clinical trial experience and considerations from experts in the field.DESIGN: Safety evaluation based on the phase 2 Ladder (NCT02510794) and phase 3 Archway (NCT03677934) trials of the PDS.METHODS: The PDS is a permanent, indwelling, and refillable ocular drug delivery system that requires standardized procedural steps, for its insertion and refill-exchange procedures, which have evolved during the PDS clinical program. We describe identified AEs that may arise after implant insertion or refill-exchange procedures, including conjunctival retraction, conjunctival erosion, endophthalmitis, implant dislocation, conjunctival bleb or conjunctival filtering bleb leak, wound leak, hypotony, choroidal detachment, vitreous hemorrhage, rhegmatogenous retinal detachment, cataract, and septum dislodgement.RESULTS: Adverse events related to the PDS were well understood, manageable by trial investigators, and did not prevent patients from achieving optimal outcomes in most cases.CONCLUSIONS: Surgeons using the PDS should be aware of potential ocular AEs and identify them early for optimal management. As with any new surgical procedure, it is important to provide surgeons with appropriate training, to ensure adherence to optimal surgical techniques, and to continually refine the procedure to mitigate complications and improve outcomes.

    View details for DOI 10.1016/j.oret.2022.05.011

    View details for PubMedID 35589078

  • Deep Learning for Glaucoma Detection and Identification of Novel Diagnostic Areas in Diverse Real-World Datasets. Translational vision science & technology Noury, E., Mannil, S. S., Chang, R. T., Ran, A. R., Cheung, C. Y., Thapa, S. S., Rao, H. L., Dasari, S., Riyazuddin, M., Chang, D., Nagaraj, S., Tham, C. C., Zadeh, R. 2022; 11 (5): 11

    Abstract

    To develop a three-dimensional (3D) deep learning algorithm to detect glaucoma using spectral-domain optical coherence tomography (SD-OCT) optic nerve head (ONH) cube scans and validate its performance on ethnically diverse real-world datasets and on cropped ONH scans.In total, 2461 Cirrus SD-OCT ONH scans of 1012 eyes were obtained from the Glaucoma Clinic Imaging Database at the Byers Eye Institute, Stanford University, from March 2010 to December 2017. A 3D deep neural network was trained and tested on this unique raw OCT cube dataset to identify a multimodal definition of glaucoma excluding other concomitant retinal disease and optic neuropathies. A total of 1022 scans of 363 glaucomatous eyes (207 patients) and 542 scans of 291 normal eyes (167 patients) from Stanford were included in training, and 142 scans of 48 glaucomatous eyes (27 patients) and 61 scans of 39 normal eyes (23 patients) were included in the validation set. A total of 3371 scans (Cirrus SD-OCT) from four different countries were used for evaluation of the model: the non overlapping test dataset from Stanford (USA) consisted of 694 scans: 241 scans from 113 normal eyes of 66 patients and 453 scans of 157 glaucomatous eyes of 89 patients. The datasets from Hong Kong (total of 1625 scans; 666 OCT scans from 196 normal eyes of 99 patients and 959 scans of 277 glaucomatous eyes of 155 patients), India (total of 672 scans; 211 scans from 147 normal eyes of 98 patients and 461 scans from 171 glaucomatous eyes of 101 patients), and Nepal (total of 380 scans; 158 scans from 143 normal eyes of 89 patients and 222 scans from 174 glaucomatous eyes of 109 patients) were used for external evaluation. The performance of the model was then evaluated on manually cropped scans from Stanford using a new algorithm called DiagFind. The ONH region was cropped by identifying the appropriate zone of the image in the expected location relative to Bruch's Membrane Opening (BMO) using a commercially available imaging software. Subgroup analyses were performed in groups stratified by eyes, myopia severity of glaucoma, and on a set of glaucoma cases without field defects. Saliency maps were generated to highlight the areas the model used to make a prediction. The model's performance was compared to that of a glaucoma specialist using all available information on a subset of cases.The 3D deep learning system achieved area under the curve (AUC) values of 0.91 (95% CI, 0.90-0.92), 0.80 (95% CI, 0.78-0.82), 0.94 (95% CI, 0.93-0.96), and 0.87 (95% CI, 0.85-0.90) on Stanford, Hong Kong, India, and Nepal datasets, respectively, to detect perimetric glaucoma and AUC values of 0.99 (95% CI, 0.97-1.00), 0.96 (95% CI, 0.93-1.00), and 0.92 (95% CI, 0.89-0.95) on severe, moderate, and mild myopia cases, respectively, and an AUC of 0.77 on cropped scans. The model achieved an AUC value of 0.92 (95% CI, 0.90-0.93) versus that of the human grader with an AUC value of 0.91 on the same subset of scans (\(P=0.99\)). The performance of the model in terms of recall on glaucoma cases without field defects was found to be 0.76 (0.68-0.85). Saliency maps highlighted the lamina cribrosa in glaucomatous eyes versus superficial retina in normal eyes as the regions associated with classification.A 3D convolutional neural network (CNN) trained on SD-OCT ONH cubes can distinguish glaucoma from normal cases in diverse datasets obtained from four different countries. The model trained on additional random cropping data augmentation performed reasonably on manually cropped scans, indicating the importance of lamina cribrosa in glaucoma detection.A 3D CNN trained on SD-OCT ONH cubes was developed to detect glaucoma in diverse datasets obtained from four different countries and on cropped scans. The model identified lamina cribrosa as the region associated with glaucoma detection.

    View details for DOI 10.1167/tvst.11.5.11

    View details for PubMedID 35551345

  • Conjunctiva and Tenon?s Capsule Handling in the Port Delivery System with Ranibizumab Implant Insertion Procedure: Surgical Pearls OPHTHALMIC SURGERY LASERS & IMAGING RETINA Graff, J. M., Sheth, V. S., Chang, R. T., Menezes, A. R., Barteselli, G., Malhotra, V. K. 2022; 53 (5): 266-273

    Abstract

    To describe conjunctiva and Tenon's capsule handling during the Port Delivery System with ranibizumab (PDS) implant insertion procedure including up-front assessments, planning, and instrumentation, with emphasis placed on the peritomy, scleral dissection, and closure steps.Surgical pearls based on experience accumulated in the PDS clinical trial program in patients with retinal diseases.Preoperative preparation, specific instruments, and meticulous techniques are key to optimizing surgical outcomes. Before surgery, assessment of factors that affect conjunctival integrity and an in-office conjunctiva examination are conducted. Gentle, purposeful conjunctiva and Tenon's capsule handling with nontoothed forceps and suturing with a BV needle are recommended to prevent tissue damage. The peritomy is 6 mm by 6 mm, centered around the planned implant location in the superotemporal quadrant. A complete sub-Tenon's capsule dissection is achieved using a wide, robust lateral and posterior dissection technique to free tissue from the sclera and minimize tension. The globe is stabilized during scleral cutdown by grasping the sclera with fine-toothed forceps away from the incision edge to prevent tissue delamination. When closing the peritomy, both the conjunctiva and Tenon's capsule are completely captured and sutured with scleral anchoring at the apex of the peritomy to help prevent conjunctival retraction and erosion. Mitigation and detection of adverse events is critical to successful surgical outcomes.The PDS implant insertion procedure is straightforward, but it requires planned preoperative preparation, specific instruments, and meticulous techniques. The surgical pearls described here offer insights for optimizing outcomes. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:266-273.].

    View details for DOI 10.3928/23258160-20220415-03

    View details for Web of Science ID 000800365300004

    View details for PubMedID 35575739

  • Implant Insertion Procedure of the Port Delivery System With Ranibizumab: Overview and Clinical Pearls OPHTHALMIC SURGERY LASERS & IMAGING RETINA Pieramici, D. J., Wieland, M. R., Stewart, J. M., Chang, R. T., Gune, S. A., Malhotra, V. K., Barteselli, G., Awh, C. C. 2022; 53 (5): 249-+

    Abstract

    To describe the Port Delivery System with ranibizumab implant insertion procedure.A surgical procedure based on the clinical trial program in patients with retinal diseases.An infusion line is placed in the infero-temporal quadrant; a superotemporal quadrant corneal traction suture is recommended. The superotemporal quadrant peritomy of 6 × 6 mm is executed with gentle, purposeful tissue handling. Generous posterior and lateral sub-Tenon's capsule dissection creates laxity for the subsequent closure. Adequate scleral hemostasis is achieved with wet-field cautery to maintain a clean field. The implant is filled under magnification with a customized formulation of ranibizumab. A precise 3.5-mm-long scleral incision (4 mm posterior and parallel to the limbus) is created to ensure proper implant fit. The exposed pars plana undergoes laser ablation to reduce vitreous hemorrhage risk. A pars plana incision is made, and the implant is inserted perpendicular to the globe and seated flush against the sclera. Complete closure of both the conjunctiva and Tenon's capsule with scleral anchoring and mild tissue overhang at the anterior limbus is performed to reduce conjunctival erosion and retraction risks.The procedure is straightforward yet requires precise preoperative and intraoperative preparation and standardized surgical techniques. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:249-256.].

    View details for DOI 10.3928/23258160-20220408-01

    View details for Web of Science ID 000800365300002

    View details for PubMedID 35575736

  • Patient Personality and Illness Perceptions in Relation to Follow-Up Appointment Adherence in Neuro-Ophthalmology. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Aziz, R., Bindiganavale, M. P., Chang, R. T., Moss, H. E. 2022

    Abstract

    BACKGROUND: Improving patient attendance at medical follow-up visits may have a notable impact on disease and overall health outcomes. Understanding factors contributing to poor attendance is important for identifying at-risk patients and designing interventions to improve clinical outcomes. Our objective was to identify personality and illness perception factors associated with attendance at recommended follow-up visits in a neuro-ophthalmology practice.METHODS: New or established patients (≥18 years) with scheduled neuro-ophthalmology (study) or glaucoma (comparison) appointments at a tertiary care academic medical center completed the Brief Illness Perception Questionnaire and Ten-Item Personality Inventory. Physician recommendations made during the visit were recorded (medications, referrals, follow-up, testing, and procedures). A chart review was performed 18 months after enrollment to assess attendance at follow-up appointment and adherence with other physician recommendations. Multiple variable logistic regression models studied associations between follow-up appointment attendance and demographic factors, appointment factors, and survey responses.RESULTS: Among 152 respondents (97% response rate (152 of 157), aged 19-97 years, 58% female, 34% new, 80 neuro-ophthalmology, 72 glaucoma), neuro-ophthalmology subjects were younger, more likely to be White, non-Hispanic, female and new to the practice than subjects with glaucoma. They reported higher emotional impact, identity, and consequences related to their illness (P = 0.001-0.03). Neuro-ophthalmology physician recommendations included more referrals to other services (17.5% vs 1.4%, P = 0.001, chi-square) and more radiology studies (15% vs 0%, P = 0.001, chi-square), but fewer follow-up visits (75% vs 97%, P < 0.0005, chi-square). Among those with recommended follow-up visits, neuro-ophthalmology subjects had lower rates of on-time appointment attendance (55% vs 77%, P = 0.009, chi-square). In a multiple variable model, on-time follow-up attendance was associated with shorter recommended follow-up interval (≤90 days, P < 0.0005), established (vs new) patient status at enrollment visit (P = 0.04), and glaucoma (P = 0.08), but not subject demographics, illness perception, or personality factors.CONCLUSIONS: Patient demographics, illness perception, and personality traits were not associated with follow-up appointment attendance and therefore unlikely to be useful for identifying patients at risk of being lost to follow-up. New neuro-ophthalmology patients with a follow-up recommended ≥90 days in advance may benefit from targeted interventions to improve follow-up appointment adherence.

    View details for DOI 10.1097/WNO.0000000000001533

    View details for PubMedID 35421870

  • American Glaucoma Society Position Paper: Information Sharing Using Established Standards is Essential to the Future of Glaucoma Care. Ophthalmology. Glaucoma Rothman, A. L., Chang, R., Kolomeyer, N. N., Turalba, A., Stein, J. D., Boland, M. V. 1800

    View details for DOI 10.1016/j.ogla.2021.12.002

    View details for PubMedID 34933142

  • Daytime napping is associated with retinal microcirculation: a large population-based study in China. Sleep Liu, X., Wang, G., Wang, X., Wang, Y., Min, Y., Zhang, J., Chang, R. T., Zhao, X., He, W., Moshfeghi, D. M., Lu, Y., Hsing, A. W., Yao, K., Zhu, S. 2021

    Abstract

    STUDY OBJECTIVES: To investigate the association between daytime napping and retinal microcirculation.METHODS: This is a cross-sectional study from a prospective population-based cohort. 2,662 participants were recruited after quota sampling. Information on napping was collected through face-to-face interviews. Retinal vascular calibers (RVCs), including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arterio-to-venous ratio (AVR), were obtained from fundus photography. Multivariate regression and restricted cubic spline curve were performed to determine the association between RVCs and daytime napping duration.RESULTS: 56.4% participants reported daytime napping regularly. Compared to no nap, daytime nap was related to higher CRAE, with nap duration of 0.5-1 h showing the most significant association. 0.5-1 h daytime nappers displayed an average of 4.18 m (95% confidence interval [CI] 2.45-5.91, p < 0.001) wider CRAE than non-nappers after adjustment. No significant association was found between CRVE and daytime napping. Moreover, individuals with 0.5-1 h daytime napping had a lower risk for AVR reduction (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.56-0.86, p = 0.001) than non-nappers. Similar association persisted in non-hypertensive population. Restricted cubic spline indicated a J-shaped relationship between AVR reduction and nap duration.CONCLUSION: Retinal microcirculation was positively associated with self-reported 0.5-1 h daytime napping. Better indicators of retinal microcirculation were probably related to nap duration in a J-shaped manner. Also, the possibly beneficial role of 0.5-1 h daytime napping on retinal microcirculation might be independent of clinically diagnosed vascular diseases.

    View details for DOI 10.1093/sleep/zsab277

    View details for PubMedID 34875091

  • A Multitask Deep-Learning System to Classify Diabetic Macular Edema for Different Optical Coherence Tomography Devices: A Multicenter Analysis. Diabetes care Tang, F., Wang, X., Ran, A., Chan, C. K., Ho, M., Yip, W., Young, A. L., Lok, J., Szeto, S., Chan, J., Yip, F., Wong, R., Tang, Z., Yang, D., Ng, D. S., Chen, L. J., Brelen, M., Chu, V., Li, K., Lai, T. H., Tan, G. S., Ting, D. S., Huang, H., Chen, H., Ma, J. H., Tang, S., Leng, T., Kakavand, S., Mannil, S. S., Chang, R. T., Liew, G., Gopinath, B., Lai, T. Y., Pang, C. P., Scanlon, P. H., Wong, T. Y., Tham, C. C., Chen, H., Heng, P., Cheung, C. Y. 2021

    Abstract

    OBJECTIVE: Diabetic macular edema (DME) is the primary cause of vision loss among individuals with diabetes mellitus (DM). We developed, validated, and tested a deep learning (DL) system for classifying DME using images from three common commercially available optical coherence tomography (OCT) devices.RESEARCH DESIGN AND METHODS: We trained and validated two versions of a multitask convolution neural network (CNN) to classify DME (center-involved DME [CI-DME], non-CI-DME, or absence of DME) using three-dimensional (3D) volume scans and 2D B-scans, respectively. For both 3D and 2D CNNs, we used the residual network (ResNet) as the backbone. For the 3D CNN, we used a 3D version of ResNet-34 with the last fully connected layer removed as the feature extraction module. A total of 73,746 OCT images were used for training and primary validation. External testing was performed using 26,981 images across seven independent data sets from Singapore, Hong Kong, the U.S., China, and Australia.RESULTS: In classifying the presence or absence of DME, the DL system achieved area under the receiver operating characteristic curves (AUROCs) of 0.937 (95% CI 0.920-0.954), 0.958 (0.930-0.977), and 0.965 (0.948-0.977) for the primary data set obtained from CIRRUS, SPECTRALIS, and Triton OCTs, respectively, in addition to AUROCs >0.906 for the external data sets. For further classification of the CI-DME and non-CI-DME subgroups, the AUROCs were 0.968 (0.940-0.995), 0.951 (0.898-0.982), and 0.975 (0.947-0.991) for the primary data set and >0.894 for the external data sets.CONCLUSIONS: We demonstrated excellent performance with a DL system for the automated classification of DME, highlighting its potential as a promising second-line screening tool for patients with DM, which may potentially create a more effective triaging mechanism to eye clinics.

    View details for DOI 10.2337/dc20-3064

    View details for PubMedID 34315698

  • Detecting progression in the center of the visual field Durbin, M. K., Callan, T., Yu, S., Chang, R., Aung, T., Conner, I. P., Lee, G. C. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Intervisit specificity of a combined retinal-ganglion cell index in glaucoma Richter, D., Callan, T., Yu, S., Durbin, M. K., Conner, I. P., Chang, R., Aung, T., Lee, G. C. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • A Multi-Task Deep-Learning System to Classify Diabetic Macular Edema for Different Optical Coherence Tomography Devices: A Multi-Center Analysis Cheung, C., Tang, F., Ran, A., Tan, G., Ting, D. W., Chen, H., Ma, H., Tang, S., Leng, T., Kakavand, S., Mannil, S. S., Chang, R., Liew, G., Gopinath, B., Wong, T. Y., Wang, X. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Phase 1b randomized controlled study of short course topical recombinant human nerve growth factor (rhNGF) for neuroenhancement in glaucoma: safety, tolerability and efficacy measure outcomes. American journal of ophthalmology Gala, B., Laurel, S., Sohail, H. M., Mariana, N., Lilia, P., Bac T, N., Sylvia L, G., Amy, D., Zhongqiu, L., Melissa, A., Tom, K., Sophia Y, W., Robert, C., Ann C, F., Yasir J, S., Jeffrey L, G. 2021

    Abstract

    No approved therapies directly target retinal ganglion cells (RGCs) for neuroprotection or neuroenhancement in glaucoma. Recombinant human nerve growth factor (rhNGF) has been shown to promote RGC survival and function in animal models of optic neuropathy. Here we evaluate safety, tolerability, and efficacy of short-term, high-dose rhNGF eye drops versus placebo in a cohort of glaucoma patients.This study is a single-center, randomized, double-masked, vehicle-controlled, parallel group study designed to assess safety and tolerability as well as short-term neuroenhancement of structure and function (Clinicaltrials.gov NCT02855450). Sixty open-angle glaucoma patients were randomized 40:20 to receive either 180 μg/ml rhNGF or vehicle control eye drops in both eyes, three times daily for 8 weeks, with a 24-week post-treatment follow-up. One eye was officially selected as the study eye, although both eyes were studied and dosed. Primary endpoints were safety, as assessed through adverse events, and tolerability, as assessed through patient reported outcomes. Secondary outcome measures included best corrected visual acuity (BCVA), Humphrey visual field (HVF), electroretinogram (ERG), and optical coherence tomography (OCT) of retinal nerve fiber layer (RNFL) thickness at baseline, after 8 weeks of treatment, and at 4 and 24 weeks after treatment (12- and 32-weeks total).Of the 60 randomized subjects, 23 were female (38%) and the average age was 66.1 years. Through week 32, there were no treatment-related serious adverse events, including no unexpectedly severe progression of optic neuropathy, no adverse events affecting ocular function or pressure, and no drug-related systemic toxicity. Topical high-dose rhNGF was tolerated well, with low level of symptom burden mainly eliciting periocular ache (in 52% of treated, 5% of placebo) and only 3 patients (7.5%) discontinuing treatment due to discomfort, out of whom 1 patient (2.5%) prematurely withdrawing from the study. There were no statistically significant differences in global indices of HVF, and no meaningful differences in total, quadrant, or clock-hour mean RNFL thickness between the groups, although both of these function and structure measures showed non-significant trends towards significance in favor of rhNGF. Real-world participant data was used to generate an estimate of cohort size needed to power subsequent studies.rhNGF is safe and tolerable in a topical 180 μg/ml formulation. Although no statistically significant short-term neuroenhancement was detected in this trial, given the strong effects of NGF in preclinical models and trends detected in this study, analysis for efficacy in a neuroprotection trial is warranted.

    View details for DOI 10.1016/j.ajo.2021.11.002

    View details for PubMedID 34780798

  • Interpreting Deep Learning Studies in Glaucoma: Unresolved Challenges. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) Lee, E. B., Wang, S. Y., Chang, R. T. 2021; 10 (3): 261-267

    Abstract

    Deep learning algorithms as tools for automated image classification have recently experienced rapid growth in imaging-dependent medical specialties, including ophthalmology. However, only a few algorithms tailored to specific health conditions have been able to achieve regulatory approval for autonomous diagnosis. There is now an international effort to establish optimized thresholds for algorithm performance benchmarking in a rapidly evolving artificial intelligence field. This review examines the largest deep learning studies in glaucoma, with special focus on identifying recurrent challenges and limitations within these studies which preclude widespread clinical deployment. We focus on the 3 most common input modalities when diagnosing glaucoma, namely, fundus photographs, spectral domain optical coherence tomography scans, and standard automated perimetry data. We then analyze 3 major challenges present in all studies: defining the algorithm output of glaucoma, determining reliable ground truth datasets, and compiling representative training datasets.

    View details for DOI 10.1097/APO.0000000000000395

    View details for PubMedID 34383718

  • Automatic Identification of Referral-Warranted Diabetic Retinopathy Using Deep Learning on Mobile Phone Images. Translational vision science & technology Ludwig, C. A., Perera, C., Myung, D., Greven, M. A., Smith, S. J., Chang, R. T., Leng, T. 2020; 9 (2): 60

    Abstract

    Purpose: To evaluate the performance of a deep learning algorithm in the detection of referral-warranted diabetic retinopathy (RDR) on low-resolution fundus images acquired with a smartphone and indirect ophthalmoscope lens adapter.Methods: An automated deep learning algorithm trained on 92,364 traditional fundus camera images was tested on a dataset of smartphone fundus images from 103 eyes acquired from two previously published studies. Images were extracted from live video screenshots from fundus examinations using a commercially available lens adapter and exported as a screenshot from live video clips filmed at 1080p resolution. Each image was graded twice by a board-certified ophthalmologist and compared to the output of the algorithm, which classified each image as having RDR (moderate nonproliferative DR or worse) or no RDR.Results: In spite of the presence of multiple artifacts (lens glare, lens particulates/smudging, user hands over the objective lens) and low-resolution images achieved by users of various levels of medical training, the algorithm achieved a 0.89 (95% confidence interval [CI] 0.83-0.95) area under the curve with an 89% sensitivity (95% CI 81%-100%) and 83% specificity (95% CI 77%-89%) for detecting RDR on mobile phone acquired fundus photos.Conclusions: The fully data-driven artificial intelligence-based grading algorithm herein can be used to screen fundus photos taken from mobile devices and identify with high reliability which cases should be referred to an ophthalmologist for further evaluation and treatment.Translational Relevance: The implementation of this algorithm on a global basis could drastically reduce the rate of vision loss attributed to DR.

    View details for DOI 10.1167/tvst.9.2.60

    View details for PubMedID 33294301

  • Intervisit repeatability of a combined retinal ganglion cell index in glaucoma Durbin, M. K., Lee, G., Yu, S., Conner, I. P., Chang, R. T., Aung, T., Callan, T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • An Open-Label Phase Ib Study to Evaluate Retinal Imaging After Short-term Use of the Balance Goggles System (BGS) in Patients with Glaucoma Li, Z., Knasel, C., Nunez, M., Beykin, G., Goldstein, A., Fisher, A. C., Singh, K., Sun, Y., Chang, R. T., Lee, W., Goldberg, J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • Comparison of Virtual Reality (PalmScan VF2000) Visual Fields Analyzer with Humphrey Visual Field in Glaucoma Patients Tran, E., Wan, L., Yan, W., Sun, Y., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • Assessing Illness Perception Factors Associated with Educational Needs in Neuro-Ophthalmology Aziz, R., Chang, R. T., Moss, H. E. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • A 3D Deep Learning System for Detecting Referable Glaucoma Using Full OCT Macular Cube Scans. Translational vision science & technology Russakoff, D. B., Mannil, S. S., Oakley, J. D., Ran, A. R., Cheung, C. Y., Dasari, S., Riyazzuddin, M., Nagaraj, S., Rao, H. L., Chang, D., Chang, R. T. 2020; 9 (2): 12

    Abstract

    The purpose of this study was to develop a 3D deep learning system from spectral domain optical coherence tomography (SD-OCT) macular cubes to differentiate between referable and nonreferable cases for glaucoma applied to real-world datasets to understand how this would affect the performance.There were 2805 Cirrus optical coherence tomography (OCT) macula volumes (Macula protocol 512 × 128) of 1095 eyes from 586 patients at a single site that were used to train a fully 3D convolutional neural network (CNN). Referable glaucoma included true glaucoma, pre-perimetric glaucoma, and high-risk suspects, based on qualitative fundus photographs, visual fields, OCT reports, and clinical examinations, including intraocular pressure (IOP) and treatment history as the binary (two class) ground truth. The curated real-world dataset did not include eyes with retinal disease or nonglaucomatous optic neuropathies. The cubes were first homogenized using layer segmentation with the Orion Software (Voxeleron) to achieve standardization. The algorithm was tested on two separate external validation sets from different glaucoma studies, comprised of Cirrus macular cube scans of 505 and 336 eyes, respectively.The area under the receiver operating characteristic (AUROC) curve for the development dataset for distinguishing referable glaucoma was 0.88 for our CNN using homogenization, 0.82 without homogenization, and 0.81 for a CNN architecture from the existing literature. For the external validation datasets, which had different glaucoma definitions, the AUCs were 0.78 and 0.95, respectively. The performance of the model across myopia severity distribution has been assessed in the dataset from the United States and was found to have an AUC of 0.85, 0.92, and 0.95 in the severe, moderate, and mild myopia, respectively.A 3D deep learning algorithm trained on macular OCT volumes without retinal disease to detect referable glaucoma performs better with retinal segmentation preprocessing and performs reasonably well across all levels of myopia.Interpretation of OCT macula volumes based on normative data color distributions is highly influenced by population demographics and characteristics, such as refractive error, as well as the size of the normative database. Referable glaucoma, in this study, was chosen to include cases that should be seen by a specialist. This study is unique because it uses multimodal patient data for the glaucoma definition, and includes all severities of myopia as well as validates the algorithm with international data to understand generalizability potential.

    View details for DOI 10.1167/tvst.9.2.12

    View details for PubMedID 32704418

    View details for PubMedCentralID PMC7347026

  • A 3D Deep Learning System for Detecting Referable Glaucoma Using Full OCT Macular Cube Scans TRANSLATIONAL VISION SCIENCE & TECHNOLOGY Russakoff, D. B., Mannil, S. S., Oakley, J. D., Ran, A., Cheung, C. Y., Dasari, S., Riyazzuddin, M., Nagaraj, S., Rao, H. L., Chang, D., Chang, R. T. 2020; 9 (2)
  • The Stanford Acuity Test: A Precise Vision Test Using Bayesian Techniques and a Discovery in Human Visual Response Piech, C., Malik, A., Scott, L. M., Chang, R. T., Lin, C., Assoc Advancement Artificial Intelligence ASSOC ADVANCEMENT ARTIFICIAL INTELLIGENCE. 2020: 471-479
  • Towards multi-center glaucoma OCT image screening with semi-supervised joint structure and function multi-task learning. Medical image analysis Wang, X. n., Chen, H. n., Ran, A. R., Luo, L. n., Chan, P. P., Tham, C. C., Chang, R. T., Mannil, S. S., Cheung, C. Y., Heng, P. A. 2020; 63: 101695

    Abstract

    Glaucoma is the leading cause of irreversible blindness in the world. Structure and function assessments play an important role in diagnosing glaucoma. Nowadays, Optical Coherence Tomography (OCT) imaging gains increasing popularity in measuring the structural change of eyes. However, few automated methods have been developed based on OCT images to screen glaucoma. In this paper, we are the first to unify the structure analysis and function regression to distinguish glaucoma patients from normal controls effectively. Specifically, our method works in two steps: a semi-supervised learning strategy with smoothness assumption is first applied for the surrogate assignment of missing function regression labels. Subsequently, the proposed multi-task learning network is capable of exploring the structure and function relationship between the OCT image and visual field measurement simultaneously, which contributes to classification performance improvement. It is also worth noting that the proposed method is assessed by two large-scale multi-center datasets. In other words, we first build the largest glaucoma OCT image dataset (i.e., HK dataset) involving 975,400 B-scans from 4,877 volumes to develop and evaluate the proposed method, then the model without further fine-tuning is directly applied on another independent dataset (i.e., Stanford dataset) containing 246,200 B-scans from 1,231 volumes. Extensive experiments are conducted to assess the contribution of each component within our framework. The proposed method outperforms the baseline methods and two glaucoma experts by a large margin, achieving volume-level Area Under ROC Curve (AUC) of 0.977 on HK dataset and 0.933 on Stanford dataset, respectively. The experimental results indicate the great potential of the proposed approach for the automated diagnosis system.

    View details for DOI 10.1016/j.media.2020.101695

    View details for PubMedID 32442866

  • Comparison of 1-Year Effectiveness of Trabecular Microbypass Stent implantation (iStent) in Conjunction With Phacoemulsification Among Mild, Moderate, and Severe Primary Open-angle Glaucoma Patients. Journal of glaucoma Chansangpetch, S. n., Ittarat, M. n., Yang, S. n., Fisher, A. C., Singh, K. n., Lin, S. C., Chang, R. T. 2020

    Abstract

    The study compared 1-year effectiveness of single trabecular microbypass stent (iStent) implantation with phacoemulsification among glaucoma severities in primary open-angle glaucoma. The study found that mild glaucoma had greater success rate and lower number of medications compared with moderate and severe glaucoma.To evaluate the effectiveness of iStent implantation in combination with cataract surgery in moderate to severe glaucoma compared with mild glaucoma.Medical charts of primary open-angle glaucoma subjects undergoing 1 iStent implantation were retrospectively reviewed. Glaucoma was classified on the basis of mean deviation (MD) of the preoperative standard automated perimetry into mild (MD>-6 dB), moderate (MD -6 to -12 dB), and severe (MD<-12 dB). Mixed effect regression models were performed to determine the effect of iStent at 1 year. The outcomes included as follows: (1) intraocular pressure (IOP) and the number of medications, (2) eyes with IOP ≤ severity-based target (18 mm Hg for mild, 15 mm Hg for moderate, 12 mm Hg for severe) (2A) without medication, and (2B) with medication reduction.In total, 104 eyes from 89 subjects were analyzed. Cataract combined with iStent surgery significantly lowered the number of medications in all groups and significantly decreased IOP in moderate and severe glaucoma (P<0.05). There was significantly higher number of medications in moderate (β: 0.58, P=0.002) and severe (β: 1.20, P<0.001) compared with mild glaucoma. Eyes with moderate glaucoma had significantly lower rate of success (criterion 2A) compared with mild glaucoma [odds ratio (OR): 0.008, P=0.047]. Eyes with moderate and severe glaucoma had significantly lower rates of success (criterion 2B) (moderate vs. mild OR: 0.002, P=0.028; severe vs. mild OR: 0.026, P=0.026).Combined phacoemulsification with iStent seems to have a better IOP-lowering and medication-lowering effect in mild glaucoma cases versus those with moderate and severe glaucoma. This difference was found in real-world data over one-year follow-up period. Long-term studies with defined IOP goals and medication removal protocols are warranted.

    View details for DOI 10.1097/IJG.0000000000001542

    View details for PubMedID 32433095

  • Comparison of Using One Trabecular Microbypass Stent versus Two during Cataract Surgery at Two Sites: One-Year Follow-Up. BioMed research international Yang, S., Ittarat, M., Tran, E., Ferrell, P., Wang, G., Fisher, A. C., Li, Z., Chang, R. T. 2020; 2020: 1920352

    Abstract

    Purpose: To compare IOP and ocular hypotensive medication reduction of using one trabecular microbypass stent versus two in patients with open-angle glaucoma. Setting. Palo Alto Veterans Affairs (VA) Hospital and the Byers Eye Institute at Stanford University, Palo Alto, California, USA.Design: Retrospective case series.Methods: A chart review included patients who underwent trabecular microbypass implantation with cataract surgery in 2015-2017, with at least one-year follow-up. Subjects were divided into two groups by location (always one stent at Stanford versus two stents at the VA). Primary outcome measures included IOP and medication reduction at baseline and 12-month follow-up.Results: 132 subjects (166 eyes) were included. The preoperative IOP was 16.3 ± 3.4mmHg on 2.6 ± 1.1 medications in the one-stent group (N = 85) and 17.5 ± 3.1mmHg on 2.7 ± 0.6 medications in the two-stent group (N = 81). There was no significant difference between the two groups (p = 0.06). At the 12-month visit, there was a 13.37% ± 2.93 reduction in IOP in the 1-stent group (p ≤ 0.001) and 13.49% ± 2.69 in the 2-stent group (p ≤ 0.001); both were not significantly different from each other (p = 0.074). At 12 months, there was also a 14.5% reduction in medication use for the 1-stent group and 15.3% reduction in the 2-stent group, both statistically significant from baseline, (p = 0.022 and p = 0.037, respectively).Conclusions: Implantation with either one or two stents during cataract surgery in patients with glaucoma demonstrated similar IOP and med reduction in both groups between the two sites.

    View details for DOI 10.1155/2020/1920352

    View details for PubMedID 32337227

  • Smartphone-Based Ophthalmic Imaging Compared to Spectral Domain Optical Coherence Tomography Assessment of Vertical Cup-to-Disc Ratio among Adults in Southwestern Uganda. Journal of glaucoma Idriss, B. R., Tran, T. M., Atwine, D. n., Chang, R. T., Myung, D. n., Onyango, J. n. 2020; Publish Ahead of Print

    Abstract

    Using optical coherence tomography measurements as a reference standard for vertical cup-to-disc ratio (vCDR), a smartphone-based ophthalmic camera has a sensitivity of 67.7% and specificity of 96.7% to detect a vCDR greater than 0.5.The purpose of this study was to assess the performance of a smartphone-based ophthalmic camera system using an Apple iPhone 6S and an adapter, Paxos Scope, to obtain adequate dilated fundus photos in order to measure clinically useful vertical cup-to-disc ratio (vCDR) cutoffs.Adult patients from a government tertiary level eye hospital in southwestern Uganda were prospectively recruited from January to April 2019. All patients experienced a comprehensive eye examination, dilated posterior segment indirect ophthalmoscope imaging with the Paxos Scope, and spectral domain optical coherence tomography (SDOCT) imaging with a Cirrus HD-OCT to measure vCDR. Patients' eyes excluded had media opacities or existing disease precluding a view of the fundus. Fundus images underwent a single masked review to assign vCDR at increments of 0.1. Descriptive statistics, parametric and Chi2 tests for significance, repeated measures correlation, kappa, receiver operating characteristics (ROC), and Bland-Altman were used to assess the data.Among 467 (consecutive) individuals, fundus photographs acquired with the Paxos Scope demonstrated a 67.7% (95%CI 63.0-72.0) sensitivity and 96.7% (95%CI 94.2-98.3) specificity to detect a vCDR >0.5, using OCT as the reference standard. 138 eyes were excluded due to poor imaging acquisition, such as dense cataract, rendering 796 eyes for analysis. The vCDR from graded Paxos Scope images and OCT correlated well with repeated measures correlation of 0.82 (95%CI, 0.77-0.86, P<0.001) and agreement, dichotomized as >0.5 or ≤0.5, was 80.9% (kappa=0.63±0.034, P<0.001). Among glaucoma and glaucoma suspects (85 eyes), the sensitivity and specificity dichotomized using vCDR >0.5 were 97.5% (95%CI, 91.3-99.7) and 80.0% (95%CI, 28.4-99.5), respectively. The area under the receiver operating characteristics curve (AROC) was 0.92 (95% CI, 0.89-0.94) for all eyes and 0.98 (95%CI, 0.78-1.0) for glaucoma and glaucoma suspects.The Paxos Scope produced images that can be reliably used to estimate vCDR, which closely aligned with the automated algorithm from OCT optic disc cube scan. The low cost, ready-to-integrate adapter, and minimal training requirements make it a viable option for population-based screening in low-resourced settings.

    View details for DOI 10.1097/IJG.0000000000001779

    View details for PubMedID 33394852

  • Detection of glaucomatous optic neuropathy with spectral-domain optical coherence tomography: a retrospective training and validation deep-learning analysis. The Lancet. Digital health Ran, A. R., Cheung, C. Y., Wang, X., Chen, H., Luo, L. Y., Chan, P. P., Wong, M. O., Chang, R. T., Mannil, S. S., Young, A. L., Yung, H. W., Pang, C. P., Heng, P. A., Tham, C. C. 2019; 1 (4): e172-e182

    Abstract

    Spectral-domain optical coherence tomography (SDOCT) can be used to detect glaucomatous optic neuropathy, but human expertise in interpretation of SDOCT is limited. We aimed to develop and validate a three-dimensional (3D) deep-learning system using SDOCT volumes to detect glaucomatous optic neuropathy.We retrospectively collected a dataset including 4877 SDOCT volumes of optic disc cube for training (60%), testing (20%), and primary validation (20%) from electronic medical and research records at the Chinese University of Hong Kong Eye Centre (Hong Kong, China) and the Hong Kong Eye Hospital (Hong Kong, China). Residual network was used to build the 3D deep-learning system. Three independent datasets (two from Hong Kong and one from Stanford, CA, USA), including 546, 267, and 1231 SDOCT volumes, respectively, were used for external validation of the deep-learning system. Volumes were labelled as having or not having glaucomatous optic neuropathy according to the criteria of retinal nerve fibre layer thinning on reliable SDOCT images with position-correlated visual field defect. Heatmaps were generated for qualitative assessments.6921 SDOCT volumes from 1 384 200 two-dimensional cross-sectional scans were studied. The 3D deep-learning system had an area under the receiver operation characteristics curve (AUROC) of 0·969 (95% CI 0·960-0·976), sensitivity of 89% (95% CI 83-93), specificity of 96% (92-99), and accuracy of 91% (89-93) in the primary validation, outperforming a two-dimensional deep-learning system that was trained on en face fundus images (AUROC 0·921 [0·905-0·937]; p<0·0001). The 3D deep-learning system performed similarly in the external validation datasets, with AUROCs of 0·893-0·897, sensitivities of 78-90%, specificities of 79-86%, and accuracies of 80-86%. The heatmaps of glaucomatous optic neuropathy showed that the learned features by the 3D deep-learning system used for detection of glaucomatous optic neuropathy were similar to those used by clinicians.The proposed 3D deep-learning system performed well in detection of glaucomatous optic neuropathy in both primary and external validations. Further prospective studies are needed to estimate the incremental cost-effectiveness of incorporation of an artificial intelligence-based model for glaucoma screening.Hong Kong Research Grants Council.

    View details for DOI 10.1016/S2589-7500(19)30085-8

    View details for PubMedID 33323187

  • Detection of glaucomatous optic neuropathy with spectral-domain optical coherence tomography: a retrospective training and validation deep-learning analysis LANCET DIGITAL HEALTH Ran, A., Cheung, C. Y., Wang, X., Chen, H., Luo, L., Chan, P. P., Wong, M. M., Chang, R. T., Mannil, S. S., Young, A. L., Yung, H., Pang, C., Heng, P., Tham, C. C. 2019; 1 (4): E172–E182
  • Dry eye and sleep quality: a large community-based study in Hangzhou. Sleep Yu, X., Guo, H., Liu, X., Wang, G., Min, Y., Chen, S. S., Han, S. S., Chang, R. T., Zhao, X., Hsing, A., Zhu, S., Yao, K. 2019

    Abstract

    STUDY OBJECTIVES: To investigate the relationship between dry eye and sleep quality in a large community-based Chinese population.METHODS: A total of 3,070 participants aged 18 to 80 were recruited from a community-based study in Hangzhou, China during 2016-2017. Sleep quality was evaluated using the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), and dry eye was evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Multivariable linear regression and logistic regression models were used to investigate the associations, adjusting for age, smoking, drinking, season, and other potential confounders.RESULTS: Overall, CPSQI score and sleep dysfunction were significantly associated with mild, moderate, and severe dry eye (ORs for CPSQI score: 1.07, 1.13, 1.14, all p<0.001; for sleep dysfunction: 1.31, 1.73, 1.66, all p<0.05). Furthermore, worse OSDI score was presented in participants with worse CPSQI score or sleep dysfunction (CPSQI score >7) (beta: 0.13, 0.54; all p<0.001). In addition, six of the seven components of CPSQI showed significant associations with dry eye (all p<0.001), except for the component of sleep medication use. Moreover, we observed significant associations of dry eye in all three subscales of OSDI with CPSQI score and sleep dysfunction.CONCLUSION: Our large, community-based study showed a strong association between poor sleep quality and an increased severity of dry eye, suggesting that preventing either one of the discomforts might alleviate the other.

    View details for DOI 10.1093/sleep/zsz160

    View details for PubMedID 31310315

  • Comparison of 1 year effectiveness of trabecular microbypass stent implantation (iStent) among mild, moderate, and severe primary open angle glaucoma Chansangpetch, S., Ittarat, M., Yang, S., Fisher, A. C., Singh, K., Lin, S. C., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • A 3D Deep Learning System for Detecting Referrable Glaucoma Using Full OCT Macular Cube Scans Russakoff, D. B., Mannil, S. S., Oakley, J. D., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Recombinant human nerve growth factor (rhNGF) eye drops for glaucoma: Results from a prospective double - masked randomized controlled trial Nunez, M., Popova, L., Nguyen, B. T., Groth, S. L., Dennis, A., Li, Z., Khavari, T., Wang, S. Y., Chang, R., Fisher, A. C., Goldberg, J. L. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Novel deep learning based algorithm for Macula and Optic Nerve Head segmentation versus Cirrus Optical Coherence Tomography in identifying glaucoma Mannil, S., Oakley, J. D., Russakoff, D. B., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Smartphone-based Retinal Imaging to Characterize Early Functional Retinal Vascular Changes in Diabetic Retinopathy Cheung, C., Wang, Y., Liu, J. K., Lai, K. W., Chang, R., Wong, T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Diagnostic Assessment of RNFL Segmentation using a Hybrid Deep Learning Approach Oakley, J. D., Mannil, S. S., Russakoff, D. B., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • A 3D Deep Learning System for Detecting Glaucomatous Optic Neuropathy from Volumetric and En Face Optical Coherence Tomography Scans Ran, A., Wang, X., Luo, L., Chan, P., Chang, R., Mannil, S., Chen, H., Heng, P., Tham, C. Y., Cheung, C. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Development and validation of a deep learning algorithm for the detection of neovascular age-related macular degeneration from color fundus photographs. Clinical & experimental ophthalmology Keel, S., Li, Z., Scheetz, J., Robman, L., Phung, J., Makeyeva, G., Aung, K. Z., Liu, C., Yan, X., Meng, W., Guymer, R., Chang, R., He, M. 2019

    Abstract

    IMPORTANCE: Detection of early onset neovascular age-related macular degeneration (AMD) is critical to protecting vision.BACKGROUND: To describe the development and validation of a deep learning algorithm (DLA) for the detection of neovascular age-related macular degeneration.DESIGN: Development and validation of a DLA using retrospective datasets.PARTICIPANTS: We developed and trained the DLA using 56,113 retinal images and an additional 86,162 images from an independent dataset to externally validate the DLA. All images were non-stereoscopic and retrospectively collected.METHODS: The internal validation dataset was derived from real-world clinical settings in China. Gold standard grading was assigned when consensus was reached by 3 individual ophthalmologists. The DLA classified 31,247 images as gradable and 24,866 as ungradable (poor quality or poor field definition). These ungradable images were used to create a classification model for image quality. Efficiency and diagnostic accuracy were tested using 86,162 images derived from the Melbourne Collaborative Cohort Study. Neovascular AMD and/or ungradable outcome in one or both eyes was considered referable.MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivity and specificity.RESULTS: In the internal validation dataset, the AUC, sensitivity and specificity of the DLA for neovascular AMD was 0.995, 96.7%, 96.4%, respectively. Testing against the independent external dataset achieved an AUC, sensitivity and specificity of 0.967, 100% and 93.4%, respectively. More than 60% of false positive cases displayed other macular pathologies. Among the false negative cases (internal validation dataset only), over half (57.2%) proved to be undetected detachment of the neurosensory retina or RPE layer.CONCLUSIONS: This DLA shows robust performance for the detection of neovascular AMD amongst retinal images from a multi-ethnic sample and under different imaging protocols. Further research is warranted to investigate where this technology could be best utilized within screening and research settings. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/ceo.13575

    View details for PubMedID 31215760

  • Characteristics of cataract surgery patients influencing patient satisfaction scores JOURNAL OF CATARACT AND REFRACTIVE SURGERY Lee, M. D., Chen, S. P., Chen, T. A., Leibold, C., Li, Z., Fisher, A., Lin, C. C., Singh, K., Chang, R. T. 2019; 45 (4): 437–42
  • Characteristics of cataract surgery patients influencing patient satisfaction scores. Journal of cataract and refractive surgery Lee, M. D., Chen, S. P., Chen, T. A., Leibold, C., Li, Z., Fisher, A. C., Lin, C. C., Singh, K., Chang, R. T. 2019

    Abstract

    PURPOSE: To determine factors that influence patient satisfaction scores in individuals who have recently had cataract surgery.SETTING: Byers Eye Institute, Palo Alto, California, USA.DESIGN: Prospective case series.METHODS: Selected questions from the Press Ganey survey and the National Eye Institute Visual Function Questionnaire-25 were administered to each patient immediately after completion of a clinic visit. The correlation between patient-specific variables and the answer to the survey question "likelihood of recommending our practice to others," a surrogate for overall patient satisfaction, was assessed using the Student t test. A logistical regression model was used to adjust for potentially confounding variables.RESULTS: One hundred forty-three patients were recruited from 4 providers; 57 (39.8%) were men, and the mean age was 70.0years±11.6 (SD). The main outcome was the proportion of scores less than 5, or "very good," for the likelihood of recommending the practice to others. There was a statistically significant association between a non-5 patient satisfaction score and self-reported ethnicity of Asian or Pacific Islandercompared with other ethnicities (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.0-5.1; P=.049); other possible correlates were not statistically significant. The relationship persisted after adjustment for potential confounding variables (OR, 2.6; 95% CI, 1.1-6.3; P=.027).CONCLUSION: In postoperative cataract patients, Asian or Pacific Islander ethnicity, a factor out of the control of the provider and clinic staff, was associated with a lower overall Press Ganey patient satisfaction score compared with patients of all other ethnicities.

    View details for PubMedID 30824352

  • Corneal Biomechanics Using a Scheimpflug-Based Noncontact Device in Normal-Tension Glaucoma and Healthy Controls. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) Hong, K., Wong, I. Y., Singh, K., Chang, R. T. 2019

    Abstract

    PURPOSE: To determine if a novel biomechanical parameter, corneal applanation velocity, as measured by the Corvis ST, is associated with a diagnosis of normal-tension glaucoma (NTG).DESIGN: Prospective, cross-sectional study.METHODS: Study and control subjects were recruited from the ophthalmology clinic of a university teaching hospital in Hong Kong over an 8-week period in 2013. A total of 80 eyes with NTG diagnosis and 155 healthy eyes randomly selected to be in the control group were included in the final analysis. All subjects underwent corneal biomechanical testing with the Oculus Corvis ST non-contact tonometer. Logistic regression analysis adjusted for age and central corneal thickness was conducted to assess the relationship between inward and outward applanation velocity and the risk of NTG. Secondary outcome variables included corneal applanation time, length, amplitude, and highest concavity.RESULTS: Inward applanation velocity was faster in the NTG eyes (0.15 ± 0.02 m/s) than in the control eyes (0.14 ± 0.02 m/s) (P = 0.016). The odds ratio for a 0.01 m/s increase in inward applanation velocity when comparing NTG eyes with control eyes adjusted for age and central corneal thickness was 1.15 (95% confidence interval, 1.03-1.30) (P = 0.016). There was no evidence that outward applanation velocity or any secondary corneal biomechanical variable differed between the NTG and control eyes.CONCLUSIONS: Normal-tension glaucoma eyes demonstrated a small, statistically significant faster corneal inward applanation velocity than normal control eyes.

    View details for PubMedID 30773853

  • Corneal Biomechanics Using a Scheimpflug-Based Noncontact Device in Normal-Tension Glaucoma and Healthy Controls ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY Hong, K., Wong, I. H., Singh, K., Chang, R. T. 2019; 8 (1): 22–29
  • Development and Validation of a Deep Learning System to Detect Glaucomatous Optic Neuropathy Using Fundus Photographs. JAMA ophthalmology Liu, H. n., Li, L. n., Wormstone, I. M., Qiao, C. n., Zhang, C. n., Liu, P. n., Li, S. n., Wang, H. n., Mou, D. n., Pang, R. n., Yang, D. n., Jiang, L. n., Chen, Y. n., Hu, M. n., Xu, Y. n., Kang, H. n., Ji, X. n., Chang, R. n., Tham, C. n., Cheung, C. n., Ting, D. S., Wong, T. Y., Wang, Z. n., Weinreb, R. N., Xu, M. n., Wang, N. n. 2019

    Abstract

    A deep learning system (DLS) that could automatically detect glaucomatous optic neuropathy (GON) with high sensitivity and specificity could expedite screening for GON.To establish a DLS for detection of GON using retinal fundus images and glaucoma diagnosis with convoluted neural networks (GD-CNN) that has the ability to be generalized across populations.In this cross-sectional study, a DLS for the classification of GON was developed for automated classification of GON using retinal fundus images obtained from the Chinese Glaucoma Study Alliance, the Handan Eye Study, and online databases. The researchers selected 241 032 images were selected as the training dataset. The images were entered into the databases on June 9, 2009, obtained on July 11, 2018, and analyses were performed on December 15, 2018. The generalization of the DLS was tested in several validation datasets, which allowed assessment of the DLS in a clinical setting without exclusions, testing against variable image quality based on fundus photographs obtained from websites, evaluation in a population-based study that reflects a natural distribution of patients with glaucoma within the cohort and an additive dataset that has a diverse ethnic distribution. An online learning system was established to transfer the trained and validated DLS to generalize the results with fundus images from new sources. To better understand the DLS decision-making process, a prediction visualization test was performed that identified regions of the fundus images utilized by the DLS for diagnosis.Use of a deep learning system.Area under the receiver operating characteristics curve (AUC), sensitivity and specificity for DLS with reference to professional graders.From a total of 274 413 fundus images initially obtained from CGSA, 269 601 images passed initial image quality review and were graded for GON. A total of 241 032 images (definite GON 29 865 [12.4%], probable GON 11 046 [4.6%], unlikely GON 200 121 [83%]) from 68 013 patients were selected using random sampling to train the GD-CNN model. Validation and evaluation of the GD-CNN model was assessed using the remaining 28 569 images from CGSA. The AUC of the GD-CNN model in primary local validation datasets was 0.996 (95% CI, 0.995-0.998), with sensitivity of 96.2% and specificity of 97.7%. The most common reason for both false-negative and false-positive grading by GD-CNN (51 of 119 [46.3%] and 191 of 588 [32.3%]) and manual grading (50 of 113 [44.2%] and 183 of 538 [34.0%]) was pathologic or high myopia.Application of GD-CNN to fundus images from different settings and varying image quality demonstrated a high sensitivity, specificity, and generalizability for detecting GON. These findings suggest that automated DLS could enhance current screening programs in a cost-effective and time-efficient manner.

    View details for DOI 10.1001/jamaophthalmol.2019.3501

    View details for PubMedID 31513266

  • Understanding Patient Attitudes Toward Multifocal Intraocular Lenses in Online Medical Forums Through Sentiment Analysis Wang, S. Y., Hernandez-Boussard, T., Chang, R. T., Pershing, S., OhnoMachado, L., Seroussi, B. IOS PRESS. 2019: 1378–82

    View details for DOI 10.3233/SHT1190453

    View details for Web of Science ID 000569653400278

  • Understanding Patient Attitudes Toward Multifocal Intraocular Lenses in Online Medical Forums Through Sentiment Analysis. Studies in health technology and informatics Wang, S. Y., Hernandez-Boussard, T. n., Chang, R. T., Pershing, S. n. 2019; 264: 1378–82

    Abstract

    Multifocal intraocular lens implants (IOLs) are a premium option for cataract surgery which patients may purchase to achieve improved spectacle-independence for near vision but may have trade-offs with visual quality. We demonstrate the use of sentiment analysis to evaluate multifocal lenses discussed on MedHelp, a leading online health forum. A search for "multifocal IOL" was performed on MedHelp.org on November 1, 2016, yielding relevant patient posts. Sentiment analysis was performed using IBM's Watson, which extracted 30,066 unique keywords and their associated sentiment scores from 7495 posts written by 1474 unique patient users. Keywords associated with monovision, monofocal, and toric lenses had positive mean sentiment, significantly higher than for keywords associated with multifocals, which had negative mean sentiment (p < 0.001, ANOVA). Many keywords represented complaints and were associated with negative sentiment, including glare, halo, and ghosting. Sentiment analysis can provide insights into patient perspectives towards multifocal lenses by interpreting online patient posts.

    View details for DOI 10.3233/SHTI190453

    View details for PubMedID 31438152

  • Ocular Antihypertensive Medication Use After iStent Implantation Concurrent With Cataract Surgery vs Cataract Surgery Alone in a Large US Health Care Claims Database JAMA OPHTHALMOLOGY Wang, S. Y., Singh, K., Stein, J. D., Chang, R. T. 2019; 137 (1): 21–27
  • An Extended Hackathon Model for Collaborative Education in Medical Innovation (vol 42, 239, 2018 ) JOURNAL OF MEDICAL SYSTEMS Wang, J. K., Pamnani, R. D., Capasso, R., Chang, R. T. 2019; 43 (1)
  • Correction to: An Extended Hackathon Model for Collaborative Education in Medical Innovation. Journal of medical systems Wang, J. K., Pamnani, R. D., Capasso, R., Chang, R. T. 2018; 43 (1): 15

    Abstract

    We append two additional funders to our acknowledgments.

    View details for PubMedID 30536040

  • An Automated Grading System for Detection of Vision-Threatening Referable Diabetic Retinopathy on the Basis of Color Fundus Photographs DIABETES CARE Li, Z., Keel, S., Liu, C., He, Y., Meng, W., Scheetz, J., Lee, P., Shaw, J., Ting, D., Wong, T., Taylor, H., Chang, R., He, M. 2018; 41 (12): 2509–16

    View details for DOI 10.2337/dc18-0147

    View details for Web of Science ID 000450560000017

  • An Extended Hackathon Model for Collaborative Education in Medical Innovation JOURNAL OF MEDICAL SYSTEMS Wang, J. K., Pamnani, R. D., Capasso, R., Chang, R. T. 2018; 42 (12)
  • Institutionalizing healthcare hackathons to promote diversity in collaboration in medicine BMC MEDICAL EDUCATION Wang, J. K., Roy, S. K., Barry, M., Chang, R. T., Bhatt, A. S. 2018; 18
  • Institutionalizing healthcare hackathons to promote diversity in collaboration in medicine. BMC medical education Wang, J. K., Roy, S. K., Barry, M., Chang, R. T., Bhatt, A. S. 2018; 18 (1): 269

    Abstract

    BACKGROUND: Medical students and healthcare professionals can benefit from exposure to cross-disciplinary teamwork and core concepts of medical innovation. Indeed, to address complex challenges in patient care, diversity in collaboration across medicine, engineering, business, and design is critical. However, a limited number of academic institutions have established cross-disciplinary opportunities for students and young professionals within these domains to work collaboratively towards diverse healthcare needs.METHODS: Drawing upon best practices from computer science and engineering, healthcare hackathons bring together interdisciplinary teams of students and professionals to collaborate, brainstorm, and build solutions to unmet clinical needs. Over the course of six months, a committee of 20 undergraduates, medical students, and physician advisors organized Stanford University's first healthcare hackathon (November 2016). Demographic data from initial applications were supplemented with responses from a post-hackathon survey gauging themes of diversity in collaboration, professional development, interest in medical innovation, and educational value. In designing and evaluating the event, the committee focused on measurable outcomes of diversity across participants (skillset, age, gender, academic degree), ideas (clinical needs), and innovations (projects).RESULTS: Demographic data (n=587 applicants, n=257 participants) reveal participants across diverse academic backgrounds, age groups, and domains of expertise were in attendance. From 50 clinical needs presented representing 19 academic fields, 40 teams ultimately formed and submitted projects spanning web (n=13) and mobile applications (n=13), artificial intelligence-based tools (n=6), and medical devices (n=3), among others. In post-hackathon survey responses (n=111), medical students and healthcare professionals alike noted a positive impact on their ability to work in multidisciplinary teams, learn from individuals of different backgrounds, and address complex healthcare challenges.CONCLUSIONS: Healthcare hackathons can encourage diversity across individuals, ideas, and projects to address clinical challenges. By providing an outline of Stanford's inaugural event, we hope more universities can adopt the healthcare hackathon model to promote diversity in collaboration in medicine.

    View details for PubMedID 30458759

  • An Extended Hackathon Model for Collaborative Education in Medical Innovation. Journal of medical systems Wang, J. K., Pamnani, R. D., Capasso, R., Chang, R. T. 2018; 42 (12): 239

    Abstract

    To support the next generation of healthcare innovators - whether they be engineers, designers, clinicians, or business experts by training - education in the emerging field of medical innovation should be made easily and widely accessible to undergraduate students, graduate students, and young professionals, early in their careers. Currently, medical innovation curricula are taught through semester-long courses or year-long fellowships at a handful of universities, reaching only a limited demographic of participants. This study describes the structure and preliminary outcomes of a 1-2week "extended hackathon" course that seeks to make medical innovation education and training more accessible and easily adoptable for academic medical centers. Eight extended hackathons were hosted in five international locations reaching 245 participants: Beijing (June 2015 and August 2016), Hong Kong (June 2016, 2017, and 2018), Curitiba (July 2016), Stanford (October 2017), and Sao Paulo (May 2018). Pre- and post-hackathon surveys asking respondents to self-assess their knowledge in ten categories of medical innovation were administered to quantify the perceived degree of learning. Participants hailed from a diverse range of educational backgrounds, domains of expertise, and academic institutions. On average, respondents (n=161) saw a greater than twofold increase (114.1%, P<0.001) from their pre- to post-hackathon scores. In this study, the extended hackathon is presented as a novel educational model to teach undergraduate and graduate students a foundational skillset for medical innovation. Participants reported gaining significant knowledge across all ten categories assessed. To more robustly assess the educational value of extended hackathons, a standardized assessment for medical innovation knowledge needs to be developed, and a larger sample size of participants surveyed.

    View details for PubMedID 30328518

  • An Automated Grading System for Detection of Vision-Threatening Referable Diabetic Retinopathy on the Basis of Color Fundus Photographs. Diabetes care Li, Z., Keel, S., Liu, C., He, Y., Meng, W., Scheetz, J., Lee, P. Y., Shaw, J., Ting, D., Wong, T., Taylor, H., Chang, R., He, M. 2018

    Abstract

    OBJECTIVE: The goal of this study was to describe the development and validation of an artificial intelligence-based, deep learning algorithm (DLA) for the detection of referable diabetic retinopathy (DR).RESEARCH DESIGN AND METHODS: A DLA using a convolutional neural network was developed for automated detection of vision-threatening referable DR (preproliferative DR or worse, diabetic macular edema, or both). The DLA was tested by using a set of 106,244 nonstereoscopic retinal images. A panel of ophthalmologists graded DR severity in retinal photographs included in the development and internal validation data sets (n = 71,043); a reference standard grading was assigned once three graders achieved consistent grading outcomes. For external validation, we tested our DLA using 35,201 images of 14,520 eyes (904 eyes with any DR; 401 eyes with vision-threatening referable DR) from population-based cohorts of Malay, Caucasian Australians, and Indigenous Australians.RESULTS: Among the 71,043 retinal images in the training and validation data sets, 12,329 showed vision-threatening referable DR. In the internal validation data set, the area under the curve (AUC), sensitivity, and specificity of the DLA for vision-threatening referable DR were 0.989, 97.0%, and 91.4%, respectively. Testing against the independent, multiethnic data set achieved an AUC, sensitivity, and specificity of 0.955, 92.5%, and 98.5%, respectively. Among false-positive cases, 85.6% were due to a misclassification of mild or moderate DR. Undetected intraretinal microvascular abnormalities accounted for 77.3% of all false-negative cases.CONCLUSIONS: This artificial intelligence-based DLA can be used with high accuracy in the detection of vision-threatening referable DR in retinal images. This technology offers potential to increase the efficiency and accessibility of DR screening programs.

    View details for PubMedID 30275284

  • Ocular Antihypertensive Medication Use After iStent Implantation Concurrent With Cataract Surgery vs Cataract Surgery Alone in a Large US Health Care Claims Database. JAMA ophthalmology Wang, S. Y., Singh, K., Stein, J. D., Chang, R. T. 2018

    Abstract

    Importance: The iStent Trabecular Micro-Bypass (Glaukos Corporation) is a minimally invasive glaucoma implant used in conjunction with cataract surgery to lower intraocular pressure.Objective: To determine whether implantation of the iStent concurrent with cataract surgery is associated with reduced use of ocular antihypertensive medications in a US health care claims database.Design, Setting, and Participants: Retrospective, observational longitudinal cohort study of individuals enrolled in a US managed care network who underwent iStent implantation with cataract surgery (iStent/CEIOL) from 2012 to 2016 (n=1509 bilateral and n=1462 unilateral surgery). A control group of individuals who underwent bilateral cataract surgery only (CEIOL) were matched 1:1 to patients undergoing bilateral iStent/CEIOL on baseline demographic and clinical factors. Data were analyzed between November 1, 2017, and January 31, 2018.Main Outcomes and Measures: The number of topical ocular antihypertensive agents used postoperatively by patients undergoing iStent/CEIOL compared with baseline and with matched CEIOL control individuals, and hazard ratios with 95% confidence intervals for sustained reduced use of at least 1 topical ocular antihypertensive agent postoperatively.Results: Of the 2971 eligible enrollees, mean age at first surgery was 74.3 years, and 1659 (55.8%) were women. Patients undergoing iStent/CEIOL had diagnoses that included primary open-angle glaucoma (n=2329; 78.4%), narrow angles (n=381; 12.8%), and secondary glaucomas (n=261; 8.8%). At baseline, 1223 (41.2%) were receiving no topical glaucoma agents; 876 (29.5%), 437 (14.7%), and 435 (14.6%) were receiving 1, 2, or at least 3 agents, respectively. Although only 678 persons (22.8%) completed at least 2 years of postoperative follow-up, the proportion of patients receiving no drops increased postoperatively (64.7%, 20-24 months, P<.001, chi2). Patients receiving at least 1 topical agent at baseline had mean reduction of 1.01 and 0.61 medications used at 20 to 24 months with bilateral or unilateral surgery, respectively (both P<.001, paired t). Sustained reduction in glaucoma medication use was more likely in patients receiving at least 3 vs 1 medication at baseline (hazard ratio, 1.68; 95% CI, 1.36-2.09). Compared with matched control individuals undergoing CEIOL, patients undergoing bilateral iStent/CEIOL had a greater mean reduction in drops used (0.99 vs 0.49; postoperative month 20-24; P<.001; paired t) and a higher proportion receiving no drops postoperatively (73.5% vs 55.3%, postoperative month 20-24; P<.001; chi2).Conclusions and Relevance: Implantation of the iStent trabecular micro-bypass stent concurrent with cataract surgery was associated with moderately reduced use of topical ocular antihypertensive medication. Reduction in the use of glaucoma medications may lessen the burden of medication adverse effects and promote better adherence.

    View details for PubMedID 30267072

  • Efficacy of a Deep Learning System for Detecting Glaucomatous Optic Neuropathy Based on Color Fundus Photographs OPHTHALMOLOGY Li, Z., He, Y., Keel, S., Meng, W., Chang, R. T., He, M. 2018; 125 (8): 1199–1206

    Abstract

    To assess the performance of a deep learning algorithm for detecting referable glaucomatous optic neuropathy (GON) based on color fundus photographs.A deep learning system for the classification of GON was developed for automated classification of GON on color fundus photographs.We retrospectively included 48 116 fundus photographs for the development and validation of a deep learning algorithm.This study recruited 21 trained ophthalmologists to classify the photographs. Referable GON was defined as vertical cup-to-disc ratio of 0.7 or more and other typical changes of GON. The reference standard was made until 3 graders achieved agreement. A separate validation dataset of 8000 fully gradable fundus photographs was used to assess the performance of this algorithm.The area under receiver operator characteristic curve (AUC) with sensitivity and specificity was applied to evaluate the efficacy of the deep learning algorithm detecting referable GON.In the validation dataset, this deep learning system achieved an AUC of 0.986 with sensitivity of 95.6% and specificity of 92.0%. The most common reasons for false-negative grading (n = 87) were GON with coexisting eye conditions (n = 44 [50.6%]), including pathologic or high myopia (n = 37 [42.6%]), diabetic retinopathy (n = 4 [4.6%]), and age-related macular degeneration (n = 3 [3.4%]). The leading reason for false-positive results (n = 480) was having other eye conditions (n = 458 [95.4%]), mainly including physiologic cupping (n = 267 [55.6%]). Misclassification as false-positive results amidst a normal-appearing fundus occurred in only 22 eyes (4.6%).A deep learning system can detect referable GON with high sensitivity and specificity. Coexistence of high or pathologic myopia is the most common cause resulting in false-negative results. Physiologic cupping and pathologic myopia were the most common reasons for false-positive results.

    View details for PubMedID 29506863

  • Automatic identification of referral-warranted diabetic retinopathy using deep learning on mobile phone images Leng, T., Greven, M., Smith, S., Ludwig, C., Chang, R., Gargeya, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Comparison of Automated Self-Refraction Using NETRA with Table-Mounted Autorefractor and Subjective Refraction in an Academic Optometry Clinic Li, Z., Leibold, C., Binder, S. W., Beyer, J., Warner, K. A., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Characteristics of cataract surgery patients influencing Press Ganey patient satisfaction scores Lee, M., Chen, S., Chen, T., Fisher, A., Lin, C. C., Singh, K., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Impact of Race on Press Ganey Measures of Ophthalmology Clinic Visits Chen, T., Chen, S., Lee, M., Fisher, A., Lin, C. C., Singh, K., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Reduction of Ocular Antihypertensive Medication Use After IStent Implantation in a Large US Managed Care Network Wang, S., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • A deep learning system for detecting glaucomatous optic neuropathy and age-related macular degeneration based on color fundus photographs He, M., Li, Z., Keel, S., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • The development and validation of a deep learning algorithm for referable diabetic retinopathy Keel, S., Li, Z., He, Y., Meng, W., Chang, R., He, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Recombinant human nerve growth factor (rhNGF) eye drops for glaucoma: Interim results Popova, L., Nunez, M., Bac Tien Nguyen, Groth, S., Dennis, A., Li, Z., Khavari, T., Wang, S., Chang, R., Fisher, A., Goldberg, J. L. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Specific Location of Disc Hemorrhage is Linked to Nerve Fiber Layer Defects. Optometry and vision science Yoo, Y. C., Kim, J. M., Park, H. S., Yoo, C., Shim, S. H., Won, Y. S., Park, K. H., Chang, R. T. 2017; 94 (6): 647-653

    Abstract

    To investigate the relationship between retinal nerve fiber layer (RNFL) defects and the quadrant and proximal location of disc hemorrhages (DHs) in a large population examined for health screening.A total of 168,044 subjects older than 20 years underwent a single screening ophthalmic examination with color fundus photography as part of a comprehensive health screening program. The presence and location of DHs and RNFL defects were assessed. The DH locations were defined according to the quadrant location (inferotemporal, superotemporal, inferonasal, or superonasal) and the most proximal end of DHs relative to the disc center (cup base, cup margin, disc rim, or extrapapillary region). Using these two location descriptors as independent variables, a logistic regression analysis was conducted to explore the effects of DH location on RNFL defects.Two hundred twenty-six eyes had DH and 120 (53.1%) of them had RNFL defects. After adjusting for proximal location, DHs located in the inferotemporal quadrant accompanied RFNL defects 12 times more frequently than those in the superonasal quadrant (odds ratio [OR], 11.81; P = .004). Conversely, after adjusting for quadrant location, the ORs for an associated RNFL defect were 3.73 (P < .001), 16.54 (P < .001), and 8.91 (P = .002) for DHs with the proximal end at the disc rim, cup margin, and cup base, respectively.Among the four quadrants and four proximal locations, DHs were identified most frequently in the inferotemporal quadrant and outside the disc, respectively. Some DH locations, such as the inferotemporal quadrant and the cup margin, were associated with RNFL defects, whereas others were not.

    View details for DOI 10.1097/OPX.0000000000001077

    View details for PubMedID 28452808

  • Three year follow-up of serial structural and function testing in high myopes without elevated intraocular pressure Au, T. J., Lee, M., Singh, K., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2017
  • Reply. Retina (Philadelphia, Pa.) He, L., Toy, B., Blumenkranz, M., Chang, R., Myung, D. 2017; 37 (6)

    View details for DOI 10.1097/IAE.0000000000001642

    View details for PubMedID 28376047

  • Deep convolutional neural networks for automated OCT pathology recognition Russakoff, D. B., Oakley, J. D., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2017
  • Serial Spectral-Domain Optical Coherence Tomography Findings in Acute Retinal Pigment Epitheliitis and the Correlation to Visual Acuity. Ophthalmology Iu, L. P., Lee, R., Fan, M. C., Lam, W., Chang, R. T., Wong, I. Y. 2017; 124 (6): 903-909

    Abstract

    To evaluate the features of acute retinal pigment epitheliitis (ARPE) at onset and in the course of recovery by serial spectral-domain optical coherence tomography (SD OCT) and the correlation to visual acuity (VA).Retrospective cohort study.Consecutive patients with ARPE.A review of medical records was performed.Integrity of SD OCT retinal bands at onset and in the course of disease, time required to achieve each retinal band restoration, corresponding VA change, and final VA.Four patients were included. Initial SD OCT showed a dome-shaped hyper-reflective lesion at the photoreceptor outer segment layer disrupting the ellipsoid zone (EZ) and interdigitation zone (IZ) (100%). In the early phase, there was also upward displacement of the external limiting membrane (ELM) and mild transient thickening of the retinal pigment epithelium (RPE)/Bruch's complex (Bc). Acute retinal pigment epitheliitis resolved in a sequence of (1) a decrease in height of SD OCT hyper-reflective lesion and the upwardly displaced ELM returning to its normal position with irregularity; (2) complete disappearance of the hyper-reflective lesion; (3) restoration of ELM; (4) restoration of EZ; and (5) restoration of IZ. The average time to restore ELM, EZ, and IZ was 4.3±5.2, 7.3±7.2, and 12.5±12.4 weeks, respectively, and the corresponding logarithm of the minimum angles of resolution (logMAR) VAs were 0.24±0.23, 0.09±0.07, and 0.05±0.06, respectively. Visual acuity improved when IZ was restored.Early SD OCT revealed an inflammatory lesion in the photoreceptor outer segment layer displacing ELM. The RPE was involved only mildly and transiently. Recovery occurred in a sequence of ELM, EZ, and IZ restoration, and VA improved when the IZ was restored. These features suggested that the IZ (i.e., the contact between photoreceptors and RPE) is the primary site of inflammation in ARPE.

    View details for DOI 10.1016/j.ophtha.2017.01.043

    View details for PubMedID 28284786

  • Training time and quality of smartphone-based anterior segment screening in rural India. Clinical ophthalmology (Auckland, N.Z.) Ludwig, C. A., Newsom, M. R., Jais, A. n., Myung, D. J., Murthy, S. I., Chang, R. T. 2017; 11: 1301–7

    Abstract

    We aimed at evaluating the ability of individuals without ophthalmologic training to quickly capture high-quality images of the cornea by using a smartphone and low-cost anterior segment imaging adapter (the "EyeGo" prototype).Seven volunteers photographed 1,502 anterior segments from 751 high school students in Varni, India, by using an iPhone 5S with an attached EyeGo adapter. Primary outcome measures were median photograph quality of the cornea and anterior segment of the eye (validated Fundus Photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department [FOTO-ED] study; 1-5 scale; 5, best) and the time required to take each photograph. Volunteers were surveyed on their familiarity with using a smartphone (1-5 scale; 5, very comfortable) and comfort in assessing problems with the eye (1-5 scale; 5, very comfortable). Binomial logistic regression was performed using image quality (low quality: <4; high quality: ≥4) as the dependent variable and age, comfort using a smartphone, and comfort in assessing problems with the eye as independent variables.Six of the seven volunteers captured high-quality (median ≥4/5) images with a median time of ≤25 seconds per eye for all the eyes screened. Four of the seven volunteers demonstrated significant reductions in time to acquire photographs (P1=0.01, P5=0.01, P6=0.01, and P7=0.01), and three of the seven volunteers demonstrated significant improvements in the quality of photographs between the first 100 and last 100 eyes screened (P1<0.001, P2<0.001, and P6<0.01). Self-reported comfort using a smartphone (odds ratio [OR] =1.25; 95% CI =1.13 to 1.39) and self-reported comfort diagnosing eye conditions (OR =1.17; 95% CI =1.07 to 1.29) were significantly associated with an ability to take a high-quality image (≥4/5). There was a nonsignificant association between younger age and ability to take a high-quality image.Individuals without ophthalmic training were able to quickly capture a high-quality magnified view of the anterior segment of the eye by using a smartphone with an attached imaging adapter.

    View details for PubMedID 28761328

  • Eye Fatigue During TV Watching: An Infrared Oculography Study of Linearly vs. Circularly Polarized LCD TV Shariati, A., Liao, K., Yu, C., Witthayaweerasak, J., Chang, R. T., Sun, M., Liao, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2016
  • Comparison of Peristat Online Perimetry with the Humphrey Perimetry in a Clinic-Based Setting TRANSLATIONAL VISION SCIENCE & TECHNOLOGY Lowry, E. A., Hou, J., Hennein, L., Chang, R. T., Lin, S., Keenan, J., Wang, S. K., Ianchulev, S., Pasquale, L. R., Han, Y. 2016; 5 (4)

    Abstract

    We determined the receiver operating characteristic (ROC) curves for Peristat online perimetry at detecting varying degrees of glaucoma and the correlation between Peristat online perimetry and Humphrey visual field.A prospective, comparative study of Peristat online perimetry (an achromatic static computer threshold testing program) and Humphrey visual field (HVF) 24-2 SITA standard testing was performed by 63 glaucoma patients and 30 healthy controls in random order. The number of total adjacent abnormal test points were identified for each test, and compared with Spearman correlation. Receive operating characteristic curves were generated for Peristat online perimetry detection of mild and moderate-severe glaucoma patients using contrast sensitivity thresholds of -16.7, -21.7, and -26.7 dB.The area under the ROC curve for glaucoma detection ranged from 0.77 to 0.81 for mild disease (mean deviation [MD], >-6 dB on HVF) and 0.85 to 0.87 for moderate to severe disease (MD, <-6 dB on HVF) depending on contrast threshold. Peristat online perimetry and Humphrey visual field abnormal points were highly correlated with Spearman rank correlations ranging from 0.55 to 0.77 (all P < 0.001).Peristat online perimetry exhibits a reasonable ROC curve without specialized equipment and exhibited significant correlation with the conventional 24° Humphrey visual field test.Low cost widely available internet-based visual fields may complement traditional office-based visual field testing.

    View details for DOI 10.1167/tvst.5.4.4

    View details for Web of Science ID 000388670600004

    View details for PubMedID 27486554

    View details for PubMedCentralID PMC4959820

  • Novel Parameter of Corneal Biomechanics That Differentiate Normals From Glaucoma JOURNAL OF GLAUCOMA Lee, R., Chang, R. T., Wong, I. Y., Lai, J. S., Lee, J. W., Singh, K. 2016; 25 (6): E603-E609

    Abstract

    To identify novel corneal biomechanical parameters differentiating glaucomatous from normal eyes.Sixty subjects with varying degrees of glaucoma severity and 61 normal controls underwent corneal biomechanical measurements including corneal deformation amplitude, inward and outward applanation length and velocity, and highest concavity time in 1 eye per subject at Queen Mary Hospital, Hong Kong. Measurements were taken with the Corvis ST device, a noncontact tonometer coupled with a high-speed Scheimpflug camera. The intraocular pressure (IOP) and central corneal thickness (CCT) were also measured.Significant findings included differences in outward applanation velocity (glaucoma: -0.37±0.01 m/s; control: -0.32±0.01 m/s; P=0.001), peak distance (glaucoma: 2.37±0.03 mm; control: 2.30±0.02 mm; P=0.005), and highest concavity time (glaucoma: 16.75±0.08 ms; control: 17.05±0.07 ms; P=0.002) between the 2 groups, after correcting for IOP, CCT, and age. Both outward applanation velocity and peak distance were moderately correlated with IOP and CCT. However, highest concavity time was not correlated with either IOP or CCT (R=0.0140 and 0.000055, respectively). Age was not correlated with any of the 3 parameters.Glaucomatous eyes have a greater mean outward applanation velocity and peak distance, but shorter time to highest concavity than eyes without glaucoma. The difference in time to highest concavity does not correlate with age, IOP, or CCT, suggesting that this parameter may be a marker of increased pressure susceptibility that is independently associated with glaucoma risk.

    View details for DOI 10.1097/IJG.0000000000000284

    View details for Web of Science ID 000379584800007

    View details for PubMedID 26035421

  • SMARTPHONE-BASED DILATED FUNDUS PHOTOGRAPHY AND NEAR VISUAL ACUITY TESTING AS INEXPENSIVE SCREENING TOOLS TO DETECT REFERRAL WARRANTED DIABETIC EYE DISEASE RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Toy, B. C., Myung, D. J., He, L., Pan, C. K., Chang, R. T., Polkinhorne, A., Merrell, D., Foster, D., Blumenkranz, M. S. 2016; 36 (5): 1000-1008

    Abstract

    To compare clinical assessment of diabetic eye disease by standard dilated examination with data gathered using a smartphone-based store-and-forward teleophthalmology platform.100 eyes of 50 adult patients with diabetes from a health care safety-net ophthalmology clinic. All patients underwent comprehensive ophthalmic examination. Concurrently, a smartphone was used to estimate near visual acuity and capture anterior and dilated posterior segment photographs, which underwent masked, standardized review. Quantitative comparison of clinic and smartphone-based data using descriptive, kappa, Bland-Altman, and receiver operating characteristic analyses was performed.Smartphone visual acuity was successfully measured in all eyes. Anterior and posterior segment photography was of sufficient quality to grade in 96 and 98 eyes, respectively. There was good correlation between clinical Snellen and smartphone visual acuity measurements (rho = 0.91). Smartphone-acquired fundus photographs demonstrated 91% sensitivity and 99% specificity to detect moderate nonproliferative and worse diabetic retinopathy, with good agreement between clinic and photograph grades (kappa = 0.91 ± 0.1, P < 0.001; AUROC = 0.97, 95% confidence interval, 0.93-1).The authors report a smartphone-based telemedicine system that demonstrated sensitivity and specificity to detect referral-warranted diabetic eye disease as a proof-of-concept. Additional studies are warranted to evaluate this approach to expanding screening for diabetic retinopathy.

    View details for Web of Science ID 000375482100029

    View details for PubMedID 26807627

  • Effectiveness of Glaucoma Counseling on Rates of Follow-up and Glaucoma Knowledge in a South Indian Population AMERICAN JOURNAL OF OPHTHALMOLOGY Do, A. T., Pillai, M. R., Balakrishnan, V., Chang, R. T., Robin, A. L., Singh, K., Lee, B. W. 2016; 163: 180-189

    Abstract

    To evaluate the impact of traditional counseling and patient-centered counseling, either alone or with recorded audio counseling reinforcement, on glaucoma knowledge and clinical follow-up.Prospective randomized controlled trial.Newly diagnosed adult glaucoma patients were randomized to one of three categories of glaucoma counseling: traditional counseling, patient-centered counseling, or patient-centered counseling with audio counseling reinforcement. Demographic and clinical information from each subject was ascertained, and all subjects completed the Glaucoma Knowledge Assessment before and after counseling sessions at the time of diagnosis and at one-month follow-up. Patients were instructed to return to clinic for routine follow-up at 1, 3, 6, 9, and 12 months after enrollment. A multivariate logistic regression model was utilized to determine factors associated with appropriate clinical follow-up.Overall, only 13.5% of subjects had appropriate clinical follow-up at one year, defined as attending at least three follow up visits during that interval, and there was no significant difference between counseling groups. The mean Glaucoma Knowledge Assessment Score (GKAS) improved by 77.6% with the initial counseling intervention (p<0.0001), decreased by 17.4% within a one-month period following initial counseling, and improved by 22.8% (p<0.001) after the second counseling intervention. Monthly household income over 2500 rupees, (GKAS) greater than 5 after initial counseling, and undergoing any ocular surgical procedure were all independent predictors of appropriate follow-up.While all three counseling methods resulted in transient improvement of patient knowledge regarding glaucomatous disease, follow-up rates were poor for all groups. Poor retention of glaucoma knowledge may impact the likelihood of patient follow up, and reinforcement with repeated counseling may be beneficial with regard to both disease knowledge and follow-up.

    View details for DOI 10.1016/j.ajo.2015.12.009

    View details for Web of Science ID 000371447500024

    View details for PubMedID 26705095

  • Assessment of corneal biomechanical parameters in myopes and emmetropes using the Corvis ST CLINICAL AND EXPERIMENTAL OPTOMETRY Lee, R., Chang, R. T., Wong, I. H., Lai, J. M., Lee, J. Y., Singh, K. 2016; 99 (2): 157-162

    View details for DOI 10.1111/cxo.12341

    View details for Web of Science ID 000640411400010

  • A novel smartphone ophthalmic imaging adapter: User feasibility studies in Hyderabad, India INDIAN JOURNAL OF OPHTHALMOLOGY Ludwig, C. A., Murthy, S. I., Pappuru, R. R., Jais, A., Myung, D. J., Chang, R. T. 2016; 64 (3): 191-200

    Abstract

    To evaluate the ability of ancillary health staff to use a novel smartphone imaging adapter system (EyeGo, now known as Paxos Scope) to capture images of sufficient quality to exclude emergent eye findings. Secondary aims were to assess user and patient experiences during image acquisition, interuser reproducibility, and subjective image quality.The system captures images using a macro lens and an indirect ophthalmoscopy lens coupled with an iPhone 5S. We conducted a prospective cohort study of 229 consecutive patients presenting to L. V. Prasad Eye Institute, Hyderabad, India. Primary outcome measure was mean photographic quality (FOTO-ED study 1-5 scale, 5 best). 210 patients and eight users completed surveys assessing comfort and ease of use. For 46 patients, two users imaged the same patient's eyes sequentially. For 182 patients, photos taken with the EyeGo system were compared to images taken by existing clinic cameras: a BX 900 slit-lamp with a Canon EOS 40D Digital Camera and an FF 450 plus Fundus Camera with VISUPAC™ Digital Imaging System. Images were graded post hoc by a reviewer blinded to diagnosis.Nine users acquired 719 useable images and 253 videos of 229 patients. Mean image quality was ≥ 4.0/5.0 (able to exclude subtle findings) for all users. 8/8 users and 189/210 patients surveyed were comfortable with the EyeGo device on a 5-point Likert scale. For 21 patients imaged with the anterior adapter by two users, a weighted κ of 0.597 (95% confidence interval: 0.389-0.806) indicated moderate reproducibility. High level of agreement between EyeGo and existing clinic cameras (92.6% anterior, 84.4% posterior) was found.The novel, ophthalmic imaging system is easily learned by ancillary eye care providers, well tolerated by patients, and captures high-quality images of eye findings.

    View details for DOI 10.4103/0301-4738.181742

    View details for Web of Science ID 000376126800003

    View details for PubMedID 27146928

  • Assessment of corneal biomechanical parameters in myopes and emmetropes using the Corvis ST CLINICAL AND EXPERIMENTAL OPTOMETRY Lee, R., Chang, R. T., Wong, I. Y., Lai, J. S., Lee, J. W., Singh, K. 2016; 99 (2): 157-162

    Abstract

    Prior studies have demonstrated conflicting results regarding the relationship between corneal biomechanical properties and refractive error. Thus, the purpose of this study was to compare the corneal biomechanical parameters of myopes and emmetropes.Ninety-four subjects with varying degrees of myopia (aged 29 to 74 years, spherical equivalent [SE] -0.5 to -17.5 D) and 25 emmetropes (aged 19 to 75 years, SE: -0.5 to +0.5 D) presenting at the Queen Mary Hospital, Hong Kong were recruited sequentially for this prospective study. All patients were phakic with no history of coexisting ocular disease. The corneal biomechanical parameters of the right eye of each subject were analysed using the Corvis ST non-contact tonometer. Intraocular pressure (IOP) was measured using both the Corvis ST and the Topcon Non-Contact Tonometer CT-80. Refractive error was measured by non-cycloplegic subjective and objective refractometry.High myopes (SE greater than -6.00 D) demonstrated greater mean outward applanation velocities (p < 0.001) and peak distance measurements (p = 0.009) compared to both low to moderate myopes (SE -0.50 to -6.00 D) and emmetropes. Both outward applanation velocity and peak distance were moderately correlated with refractive error (p ≤ 0.001), strongly correlated with IOP and weakly correlated with central corneal thickness. There were no statistically significant differences in age, IOP or central corneal thickness among emmetropes, low to moderate myopes or high myopes.Within this study of Chinese subjects, high myopes demonstrate greater corneal mean outward applanation velocity on Corvis ST testing, than emmetropes. In particular, those with high myopia (SE greater than -6.00 D) show a distinct corneal biomechanical profile relative to those with either emmetropia or low to moderate myopia using the Corvis ST.

    View details for DOI 10.1111/cxo.12341

    View details for Web of Science ID 000373392400010

    View details for PubMedID 26893029

  • Factors Associated with Patient Press Ganey Satisfaction Scores for Ophthalmology Patients. Ophthalmology Long, C., Tsay, E. L., Jacobo, S. A., Popat, R., Singh, K., Chang, R. T. 2016; 123 (2): 242-247

    Abstract

    To determine which metrics from the Press Ganey patient satisfaction survey best correlate with "likelihood to recommend" among patients in an academic tertiary medical center practice setting.Cross-sectional study.Over a 3-month period, patients presenting to an academic practice who agreed to participate were enrolled in the study if they met the following entry criteria: (1) age ≥18 years, (2) ability to read and speak English, and (3) followed in this practice between 4 months and 4 years. A total of 196 patients were recruited.A 26-item abridged version of the Press Ganey survey typically distributed to patients via mail or e-mail after visiting the Stanford University Hospital was administered privately to each eligible patient of 2 different attending clinics at the conclusion of his or her visit. The 26 survey items were not modified for the purposes of the study and were administered such that participants could not be individually identified. The arithmetic mean score for the item "Likelihood of your recommending our practice to others" was calculated by assigning a value (0-100) to the Likert value associated with survey responses and correlated with the 25 other items using the differences in the mean scores.Response to survey items graded on a 1 to 5 standard Likert scale.The weighted mean patient survey score for the "likelihood to recommend" item for the junior faculty member was 95.9% and for the senior faculty member was 94.5%, respectively. For the remaining 25 items, "Amount of time the care provider spent with you" (Diff[1-2]=1.03; P < 0.0001) and "Ease of scheduling your appointment" (Diff[1-2]=0.99; P < 0.0001) best correlated with likelihood to recommend. In contrast, "Friendliness/courtesy of the care provider" (Diff[1-2]=0.29; P = 0.0045) correlated least with likelihood to recommend. Stratification based on provider did not affect the study results.The perception of time spent with the practitioner and ease of appointment scheduling are the 2 variables that best correlate with patients recommending their ophthalmologists to other prospective patients.

    View details for DOI 10.1016/j.ophtha.2015.09.044

    View details for PubMedID 26545321

  • Reversible Conjunctival Pigmentation Associated With Prostaglandin Use JOURNAL OF GLAUCOMA Choi, D. Y., Chang, R. T., Yegnashankaran, K., Friedman, N. J. 2016; 25 (1): E56-E57

    Abstract

    A 54-year-old Indian male with a diagnosis of ocular hypertension was started on a prostaglandin analog (PGA) in both eyes to lower intraocular pressure. Six years later, he developed progressively increasing bilateral limbal conjunctival hyperpigmentation. Travoprost was discontinued and replaced with brinzolamide and over the next year, the patient's conjunctival pigmentation improved significantly in both the eyes. This case report documents with slit-lamp photography the first case of conjunctival pigmentation associated with PGA use that has been shown to have reversal with discontinuation of the PGA. Because of the widespread use of PGAs, and the evolving nature of the conjunctival pigmentation, clinicians should be aware of this reversible condition when considering biopsy or removal of conjunctival melanocytic lesions.

    View details for DOI 10.1097/IJG.0000000000000255

    View details for Web of Science ID 000374819400013

    View details for PubMedID 25967530

  • Visual field defect classification in the Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Registry Study. The British journal of ophthalmology Ding, X. n., Chang, R. T., Guo, X. n., Liu, X. n., Johnson, C. A., Holden, B. A., He, M. n. 2016

    Abstract

    To describe a new combined myopia and glaucoma visual field classification system in order to report the visual field defects in a population of mostly young Chinese high myopes aged 7-70 years.A total of 1434 visual fields (including confirmatory repeats of abnormal defects) from 487 high myopes (sphere ≤-6.0 D) were analysed from the prospective Zhongshan Ophthalmic Center-Brien Holden Vision Institute (ZOC-BHVI) High Myopia Registry Study. The predefined classification definitions covering high myopia and glaucoma categories were: normal, enlarged blind spot, abnormal suspect and abnormal with nine subtypes. Two independent graders reviewed the first 150 of 1434 fields for initial grading calibration and the remaining 1284 fields were used to assess intergrader agreement. For the percentage distribution of visual fields, the repeats and unreliable fields were excluded, leaving 894 fields.The intergrader agreement of this combined classification system was a κ value of 0.61 (95% CI 0.59 to 0.63). Among the 894 unique fields, the most common visual field was normal at 33.7% followed by enlarged blind spot at 25.6%. The per cent of 'arcuate-like' field defects (combining nasal step, early arcuate and advanced arcuate) was 16.1% with advanced arcuate at 3.4%.A proposed combined visual field classification for high myopia and glaucoma demonstrates acceptable intergrader agreement. A total of 16.1% of defects in young high myopes were found to mimic classic glaucomatous defects. These subjects are being followed prospectively to assess which ones will progress to differentiate myopic from glaucomatous field defects.

    View details for PubMedID 27033693

  • Effectiveness of glaucoma counseling on patient follow-up rates and glaucoma knowledge in a South Indian population Do, A., Singh, K., Pilai, M., Balakrishnan, V., Chang, R., Lee, B. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2015
  • Quantitative Measurement of Fixation Stability During RareBit Perimetry and Humphrey Visual Field Testing. Journal of glaucoma Lin, S. R., Lai, I. N., Dutta, S., Singh, K., Chang, R. T. 2015; 24 (2): 100-104

    Abstract

    To compare fixation stability and fixation loss between the Humphrey Field Analyzer (HVF, static fixation target) and the RareBit computer-based perimeter (RBP, kinetic fixation target) during visual field testing.Fourteen healthy volunteer subjects wore an ASL Mobile Gaze Tracker as they completed HVF 10-2 and RareBit central field tests in a random order. Fixation stability, defined as the average distance from the fixation target to the subject's gaze location, was calculated using data from the processed video capture. Fixation loss, defined as eye closure or a deviation of >20 degrees from the fixation target, was also measured. All subjects were surveyed regarding test preference.Use of the RBP kinetic target was associated with 18% improved fixation stability compared with the HVF static target (P=0.02). Nine of 14 study subjects demonstrated better fixation with RBP compared with HVF. Subjects demonstrated decreased fixation loss during RBP (0.9 s) compared with HVF (10.0 s) (P=0.002). Eighty-six percent of study subjects preferred RBP over HVF.Use of the RBP kinetic fixation target is associated with consistent fixation stability and decreased fixation loss compared with the HVF static target. This improvement in fixation stability may result from decreased perception interference (Ganzfeld, Troxler, and binocular rivalry effects), and may help account for the greater comfort reported with RBP compared with HVF.

    View details for DOI 10.1097/IJG.0b013e31829d9b41

    View details for PubMedID 25642647

  • Effectiveness of low vision services in improving patient quality of life at Aravind Eye Hospital. Indian journal of ophthalmology Do, A. T., Ilango, K., Ramasamy, D., Kalidasan, S., Balakrishnan, V., Chang, R. T. 2014; 62 (12): 1125-1131

    Abstract

    In India, where the heavy burden of visual impairment exists, low vision services are scarce and under-utilized.Our study was designed to survey the effectiveness of low vision exams and visual aids in improving patient quality of life in southern rural India.The low vision quality of life (LVQOL) questionnaire measures vision-related quality of life through 25 questions on a Likert scale of 0-5 that pertain to (1) mobility, distance vision, and lighting; (2) psychological adjustment; (3) reading and fine work; and (4) activities of daily living. This tool was translated into Tamil and verbally administered to 55 new low vision referral patients before their first visit at the low vision clinic at Aravind Eye Hospital. Low vision aids (LVAs) were prescribed at the discretion of the low vision specialist. 1-month later, the same questionnaire was administered over the phone.About 44 of 55 low vision patients completed baseline and follow-up LVQOL surveys, and 30 normal vision controls matched for age, gender, and education were also surveyed (average 117.34 points). After the low vision clinic visit, the low vision group demonstrated a 4.55-point improvement in quality of life (from 77.77 to 82.33 points, P = 0.001). Adjusting for age, gender, and education, the low vision patients who also received LVAs (n = 24) experienced an even larger increase than those who did not (n = 20) (8.89 points, P < 0.001).Low vision services and visual aids can improve the quality of life in South Indian rural population regardless of age, gender, and education level. Thus, all low vision patients who meet the criteria should be referred for evaluation.

    View details for DOI 10.4103/0301-4738.149130

    View details for PubMedID 25579355

    View details for PubMedCentralID PMC4313491

  • Parallel rarebits: A novel, large-scale visual field screening method. Clinical & experimental optometry : journal of the Australian Optometrical Association Lin, S. R., Fijalkowski, N., Lin, B. R., Li, F., Singh, K., Chang, R. T. 2014; 97 (6): 528-33

    Abstract

    Rarebit perimetry (RBP) is a computer-based perimetric testing program with sensitivity and specificity for detection of visual field defects comparable to traditional automated perimetry. To make large-scale screening more efficient, we developed a parallel rarebit perimetric method to screen groups of subjects simultaneously. We then used this method to report the mean hit rate (MHR) among subjects aged 13 to 19 years.Rarebit perimetry was installed on computers in an existing school computer laboratory. All subjects provided medical and demographic information and underwent a basic visual examination. Testing instructions were provided to groups of up to 35 subjects and rarebit perimetry was subsequently administered. Two or three test supervisors answered questions and ensured that subjects were well aligned with their test screens. Mean hit rate, reaction times, error rates and testing time were calculated, and time estimates for rarebit, frequency doubling perimetry and Humphrey 24-2 Swedish Interactive Thresholding Algorithm (SITA) fast test were compared.A total of 364 rarebit perimetric tests were conducted on 182 subjects. Of these, 154 subjects met our inclusion criteria for the reference range (three testing errors or less and visual acuity 6/9 or better). The average mean hit rate was 94.3 ± 4.63 per cent. Screening of 500 subjects using this parallel rarebit perimetric method would require approximately nine hours, which is far less than an estimated 77 hours required for frequency doubling perimetry C-20 screening tests or an estimated 127 hours required for Humphrey 24-2 SITA fast tests.Using our methods, rarebit perimetry can be administered in parallel to groups of subjects. The mean hit rate was comparable to that reported in previously published studies. This parallel technique may improve the efficiency of large-scale visual field screenings.

    View details for DOI 10.1111/cxo.12221

    View details for PubMedID 25331077

  • Optic nerve pit-associated choroidal cleft. JAMA ophthalmology Silva, R. A., Chang, R. T., Moshfeghi, D. M., Leng, T. 2014; 132 (9): 1142-?

    View details for DOI 10.1001/jamaophthalmol.2014.174

    View details for PubMedID 25058335

  • Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection. Journal of glaucoma Mwanza, J. C., Warren, J. L., Hochberg, J. T., Budenz, D. L., Chang, R. T., Ramulu, P. Y. 2014

    Abstract

    To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination.One hundred ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike's information criterion (AIC), and prediction confidence interval lengths.For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDx-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT×NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single-variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAP-FDT, and interaction GDx-TSNIT×NAP-FDT consistently provided better discriminating abilities for detecting early, moderate, and severe glaucoma than the best single-variable models.The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDx-TSNIT×NAP-FDT provides the best glaucoma prediction compared with all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared with using GDx or FDT alone.

    View details for DOI 10.1097/IJG.0000000000000065

    View details for PubMedID 24777046

  • Diagnostic performance of optical coherence tomography ganglion cell-inner plexiform layer thickness measurements in early glaucoma. Ophthalmology Mwanza, J., Budenz, D. L., Godfrey, D. G., Neelakantan, A., Sayyad, F. E., Chang, R. T., Lee, R. K. 2014; 121 (4): 849-854

    Abstract

    To evaluate the glaucoma diagnostic performance of ganglion cell inner-plexiform layer (GCIPL) parameters used individually and in combination with retinal nerve fiber layer (RNFL) or optic nerve head (ONH) parameters measured with Cirrus HD-OCT (Carl Zeiss Meditec, Inc, Dublin, CA).Prospective cross-sectional study.Fifty patients with early perimetric glaucoma and 49 age-matched healthy subjects.Three peripapillary RNFL and 3 macular GCIPL scans were obtained in 1 eye of each participant. A patient was considered glaucomatous if at least 2 of the 3 RNFL or GCIPL scans had the average or at least 1 sector measurement flagged at 1% to 5% or less than 1%. The diagnostic performance was determined for each GCIPL, RNFL, and ONH parameter as well as for binary or-logic and and-logic combinations of GCIPL with RNFL or ONH parameters.Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR).Among GCIPL parameters, the minimum had the best diagnostic performance (sensitivity, 82.0%; specificity, 87.8%; PLR, 6.69; and NLR, 0.21). Inferior quadrant was the best RNFL parameter (sensitivity, 74%; specificity, 95.9%; PLR, 18.13; and NLR, 0.27), as was rim area (sensitivity, 68%; specificity, 98%; PLR, 33.3; and NLR, 0.33) among ONH parameters. The or-logic combination of minimum GCIPL and average RNFL provided the overall best diagnostic performance (sensitivity, 94%; specificity, 85.7%; PRL, 6.58; and NLR, 0.07) as compared with the best RNFL, best ONH, and best and-logic combination (minimum GCIPL and inferior quadrant RNFL; sensitivity, 64%; specificity, 100%; PLR, infinity; and NPR, 0.36).The binary or-logic combination of minimum GCIPL and average RNFL or rim area provides better diagnostic performances than those of and-logic combinations or best single GCIPL, RNFL, or ONH parameters. This finding may be clinically valuable for the diagnosis of early glaucoma.

    View details for DOI 10.1016/j.ophtha.2013.10.044

    View details for PubMedID 24393348

  • Corneal Applanation Velocity as a Risk Factor for Normal Tension Glaucoma Hong, K., Chang, R., Wong, I., Singh, K. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2014
  • iPhone Photography of Eye Pathology for Remote Triage He, L., Myung, D., Pershing, S., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2014
  • Corneal changes after a single session of selective laser trabeculoplasty for open-angle glaucoma EYE Lee, J. W., Chan, J. C., Chang, R. T., Singh, K., Liu, C. C., Gangwani, R., Wong, M. O., Lai, J. S. 2014; 28 (1): 47-52

    Abstract

    To investigate the changes in endothelial cell count, central corneal thickness (CCT), and refractive error after a session of selective laser trabeculoplasty (SLT) for open angle glaucoma (OAG).This prospective cohort study recruited 111 eyes of 66 consecutive subjects with OAG. Subjects received SLT to 360° of the trabecular meshwork. Endothelial cell count, CCT, and spherical equivalent were measured at baseline before SLT as well as at 1 week and 1 month post SLT. A repeated measure nested ANOVA with Tukey's multiple comparison test was performed to compare the outcome measures before and after SLT.In 111 eyes of 66 subjects, the mean number of laser applications per treatment was 166.9 ± 41.4 with a mean energy level of 1.0 ± 0.07 mJ. The mean endothelial cell count decreased significantly from 2465.0 ± 334.0 cells/mm(2) at baseline to 2355.0 ± 387.0 cells/mm(2) at 1 week (P=0.0004) but increased to baseline levels at 1 month post SLT (2424.0 ± 379.4 cells/mm(2), P=0.3). The CCT, which decreased from a baseline of 549.4 ± 37.6 to 543.9 ± 40.2 μm at 1 week post SLT (P=0.02), also returned to the baseline level by 1 month (P=0.2). The spherical equivalent was static from baseline. A positive correlation was found between total laser energy and CCT at 1 month post treatment (r=0.3, P=0.005).The transient reductions in endothelial cell count and CCT following SLT returned to baseline levels 1 month after the procedure. Patients undergoing SLT should be aware of the risk of potential corneal changes.

    View details for DOI 10.1038/eye.2013.231

    View details for Web of Science ID 000329440100008

    View details for PubMedID 24136571

    View details for PubMedCentralID PMC3890760

  • An emerging treatment option for glaucoma: Rho kinase inhibitors. Clinical ophthalmology (Auckland, N.Z.) Wang, S. K., Chang, R. T. 2014; 8: 883-890

    Abstract

    Rho kinase (ROCK) inhibitors are a novel potential class of glaucoma therapeutics with multiple compounds currently in Phase II and III US Food and Drug Administration trials in the United States. These selective agents work by relaxing the trabecular meshwork through inhibition of the actin cytoskeleton contractile tone of smooth muscle. This results in increased aqueous outflow directly through the trabecular meshwork, achieving lower intraocular pressures in a range similar to prostaglandins. There are also animal studies indicating that ROCK inhibitors may improve blood flow to the optic nerve, increase ganglion cell survival, and reduce bleb scarring in glaucoma surgery. Given the multiple beneficial effects for glaucoma patients, ROCK inhibitors are certainly a highly anticipated emerging treatment option for glaucoma.

    View details for DOI 10.2147/OPTH.S41000

    View details for PubMedID 24872673

    View details for PubMedCentralID PMC4025933

  • Simple, Low-Cost Smartphone Adapter for Rapid, High Quality Ocular Anterior Segment Imaging: A Photo Diary Journal of Mobile Technology and Medicine Myung, D., Jais, A., He, L., Chang, R. T. 2014; 3 (1)
  • The Prevalence of Cirrus SD-OCT Ganglion Cell Segmentation Errors in High Myopes Johung, T., Oakley, J., Russako, D., Sabhlok, S., Li, F., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2013
  • Novel Corneal Biomechanical Parameters in Myopes vs Emmetropes Lee, R., Chang, R., Wong, I., Lai, J., Lee, J., Singh, K. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2013
  • Diagnostic Efficacy of RNFL Thickness Sectors for Glaucoma Detection Lee, G., Budenz, D., Chang, R., Crandall, A., Girkin, C., Leung, C., Neelakantan, A., Peace, J., Werner, J., Wollstein, G. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2013
  • Clinical Utility of Web-based Office and Home Peristat for the Detection of Visual Field Defects in Patients with Glaucoma Wang, S., Hou, J., Ianchulev, S., Chon, B., Han, Y., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2013
  • Analyzing Shape Parameterization of SD-OCT Optic Nerve Head Images in High Myopes as a Predictor of Visual Field Defects Sabhlok, S., Russako, D., Johung, T., Oakley, J., Li, F., Singh, K., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2013
  • Comparison of Web-based Perimetry and office-based Humphrey Visual Field (HVF) in Patients with Glaucoma Hou, J., Wang, S., Keenan, J., Chon, B., Subramanian, N., Ianchulev, T., Stamper, R., Chang, R., Han, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2013
  • Myopia and glaucoma: diagnostic and therapeutic challenges CURRENT OPINION IN OPHTHALMOLOGY Chang, R. T., Singh, K. 2013; 24 (2): 96-101

    Abstract

    There is strong epidemiologic evidence linking myopia with glaucomatous disease, but a myopic optic nerve can pose significant challenges with regard to making the correct diagnosis of glaucoma. This review provides an overview of these diagnostic and therapeutic challenges with a particular focus on how the growing prevalence of myopia among specific populations may impact such therapy.For a given individual, the link between myopia and glaucoma remains murky in many circumstances, largely because of the fact that it is difficult to separate out myopia-related structural and functional abnormalities from 'true' glaucomatous changes. Using optical coherence tomography (OCT) imaging, myopia has been found to be associated with temporal displacement and thinning of the superior and inferior nerve fiber layer bundles. In particular, sequential generations of 'Asian' ethnicities have been noted to demonstrate increasing rates of high myopia at earlier ages, sometimes with associated visual field defects at normal intraocular pressures. As is the case with any progressive condition, it is often not possible to distinguish glaucomatous from nonglaucomatous disease based on a single examination, and thus follow-up with OCT or perimetry from an established baseline is useful.Although myopia is a known risk factor for glaucoma, it may also result in structural and functional defects that cannot be distinguished from those caused by glaucoma based solely on cross-sectional information. Longitudinal observation may be necessary to distinguish among the multiple effects of myopia on the optic nerve and the natural history of glaucoma, which may vary substantially amongst those who are affected.

    View details for DOI 10.1097/ICU.0b013e32835cef31

    View details for Web of Science ID 000317039900002

    View details for PubMedID 23542349

  • VITREO-RETINAL INTERFACE SEGMENTATION FROM SPECTRAL-DOMAIN OCT USING CHANGE DETECTION AND BELIEF PROPAGATION Lu, W., Oakley, J., Russakoff, D., Chang, R., IEEE IEEE. 2013: 1320–23
  • Timely cataract surgery for improved glaucoma management JOURNAL OF CATARACT AND REFRACTIVE SURGERY Chang, R. T., Shingleton, B. J., Singh, K. 2012; 38 (10): 1709-1710

    View details for DOI 10.1016/j.jcrs.2012.08.030

    View details for Web of Science ID 000309736500002

    View details for PubMedID 22999597

  • Glaucoma Diagnostic Accuracy of Ganglion Cell-Inner Plexiform Layer Thickness: Comparison with Nerve Fiber Layer and Optic Nerve Head OPHTHALMOLOGY Mwanza, J., Durbin, M. K., Budenz, D. L., Sayyad, F. E., Chang, R. T., Neelakantan, A., Godfrey, D. G., Carter, R., Crandall, A. S. 2012; 119 (6): 1151-1158

    Abstract

    To determine the diagnostic performance of macular ganglion cell-inner plexiform layer (GCIPL) thickness measured with the Cirrus high-definition optical coherence tomography (HD-OCT) ganglion cell analysis (GCA) algorithm (Carl Zeiss Meditec, Dublin, CA) to discriminate normal eyes and eyes with early glaucoma and to compare it with that of peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) measurements.Evaluation of diagnostic test or technology.Fifty-eight patients with early glaucoma and 99 age-matched normal subjects.Macular GCIPL and peripapillary RNFL thicknesses and ONH parameters were measured in each participant, and their diagnostic abilities were compared.Area under the curve (AUC) of the receiver operating characteristic.The GCIPL parameters with the best AUCs were the minimum (0.959), inferotemporal (0.956), average (0.935), superotemporal (0.919), and inferior sector (0.918). There were no significant differences between these AUCs and those of inferior quadrant (0.939), average (0.936), and superior quadrant RNFL (0.933); vertical cup-to-disc diameter ratio (0.962); cup-to-disc area ratio (0.933); and rim area (0.910), all P>0.05.The ability of macular GCIPL parameters to discriminate normal eyes and eyes with early glaucoma is high and comparable to that of the best peripapillary RNFL and ONH parameters.Proprietary or commercial disclosure may be found after the references.

    View details for DOI 10.1016/j.ophtha.2011.12.014

    View details for Web of Science ID 000304717100010

    View details for PubMedID 22365056

  • Macular Ganglion Cell-Inner Plexiform Layer: Automated Detection and Thickness Reproducibility with Spectral Domain-Optical Coherence Tomography in Glaucoma INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Mwanza, J., Oakley, J. D., Budenz, D. L., Chang, R. T., Knight, O. J., Feuer, W. J. 2011; 52 (11): 8323-8329

    Abstract

    To demonstrate the capability of SD-OCT to measure macular retinal ganglion cell-inner plexiform layer (GCIPL) thickness and to assess its reproducibility in glaucomatous eyes.Fifty-one glaucomatous eyes (26 mild, 11 moderate, 14 severe) of 51 patients underwent macular scanning using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) macula 200×200 acquisition protocol. Five scans were obtained on 5 days within 2 months. The ganglion cell analysis (GCA) algorithm was used to detect the macular GCIPL and to measure the thickness of the overall average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL. The reproducibility of the measurements was evaluated with intraclass correlation coefficients (ICCs), coefficients of variation (COVs), and test-retest standard deviations (TRTSDs).Segmentation and measurement of GCIPL thickness were successful in 50 of 51 subjects. All ICCs ranged between 0.94 and 0.98, but ICCs for average and superior GCIPL parameters (0.97-0.98) were slightly higher than for inferior GCIPL parameters (0.94-0.97). All COVs were <5%, with 1.8% for average GCIPL and COVs for superior GCIPL parameters (2.2%-3.0%) slightly lower than those for inferior GCIPL parameters (2.5%-3.6%). The TRTSD was lowest for average GCIPL (1.16 μm) and varied from 1.43 to 2.15 μm for sectoral GCIPL CONCLUSIONS: The Cirrus HD-OCT GCA algorithm can successfully segment macular GCIPL and measure GCIPL thickness with excellent intervisit reproducibility. Longitudinal monitoring of GCIPL thickness may be possible with Cirrus HD-OCT for assessing glaucoma progression.

    View details for DOI 10.1167/iovs.11-7962

    View details for Web of Science ID 000296907700012

    View details for PubMedID 21917932

  • Myopia and glaucoma. International ophthalmology clinics Chang, R. T. 2011; 51 (3): 53-63

    View details for DOI 10.1097/IIO.0b013e31821e5342

    View details for PubMedID 21633238

  • Reproducibility of Peripapillary Retinal Nerve Fiber Layer Thickness and Optic Nerve Head Parameters Measured with Cirrus HD-OCT in Glaucomatous Eyes INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Mwanza, J., Chang, R. T., Budenz, D. L., Durbin, M. K., Gendy, M. G., Shi, W., Feuer, W. J. 2010; 51 (11): 5724-5730

    Abstract

    To assess the reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters measured with Cirrus HD-OCT in glaucomatous eyes.Fifty-five glaucomatous eyes were included in the study. The optic disc cube 200 × 200 protocol was used to obtain three scans during the same visit to evaluate the intravisit reproducibility. One scan on 4 additional days within a 2-month period of the first session was obtained to assess intervisit reproducibility. Intraclass correlation coefficient (ICC), coefficient of variation (CV), and test-retest SD (TRT SD) were calculated for each RNFL and ONH parameter. The formula 1.645 × √2 × intervisit TRT SD provides an upper tolerance limit to variability beyond which nonphysiologic change should be considered.All ICCs were excellent, ranging from 83.9% to 99.2% for intravisit measurements and from 80.8% to 99.1% for intervisit measurements. Cup/disc area ratio had the lowest CV (1.1%) in either type of measurement, followed by average RNFL thickness (1.9% and 2.7%). Nasal clock hours and quadrants showed the poorest reproducibility as did the clock hour directly temporally. The intervisit tolerance limit for average RNFL thickness was 3.89 μm.Intravisit and intervisit measurements of peripapillary RNFL thickness and ONH parameters with Cirrus HD-OCT showed excellent reproducibility, indicating that this instrument may be useful in monitoring glaucoma progression. When comparing two measurements from the same eye on two different visits, a reproducible decrease in average RNFL thickness of approximately 4 μm or more may be considered a statistically significant change from baseline.

    View details for DOI 10.1167/iovs.10-5222

    View details for Web of Science ID 000283558400041

    View details for PubMedID 20574014

  • The Utility of the Monocular Trial Data from the Ocular Hypertension Treatment Study OPHTHALMOLOGY Bhorade, A. M., Wilson, B. S., Gordon, M. O., Palmberg, P., Weinreb, R. N., Miller, E., Chang, R. T., Kass, M. A. 2010; 117 (11): 2047-2054

    Abstract

    To determine whether adjusting the intraocular pressure (IOP) change of the trial eye for the IOP change of the fellow eye (i.e., monocular trial) is a better assessment of medication response than testing each eye independently.Analysis of data from a prospective, randomized, clinical trial.Two hundred six participants with ocular hypertension randomized to the observation group and later started on a topical prostaglandin analog (PGA).Participants were started on a topical PGA in 1 eye and returned in approximately 1 month to determine medication response. The IOP response of the trial eye was determined by the IOP change between baseline and 1 month in the trial eye alone (unadjusted method) and by adjusting for the IOP change in the fellow eye between the same visits (adjusted method). Our "gold standard" for medication response was the IOP change in the trial eye between up to 3 pre- and 3 posttreatment visits on the same medication. Pearson correlation was used to compare the gold standard with the unadjusted and adjusted methods. In addition, symmetry of IOP response between trial and fellow eyes to the same medication was determined by correlating the trial eye IOP change between up to 3 pre- and 3 posttreatment visits to the fellow eye IOP change between the same visits.Correlations of IOP change of the trial eye using the gold standard to the IOP change of the trial eye using the unadjusted and adjusted methods.The correlations of IOP change using the gold standard to the IOP change using the unadjusted and adjusted methods were r = 0.40 and r = 0.41, respectively. The correlation of IOP change of both eyes between the same pre- and posttreatment visits was r = 0.81.The monocular trial (i.e., adjusted method) appears equivalent to testing each eye independently (i.e., unadjusted method); however, neither method is adequate to determine medication response to topical PGAs. Both eyes have a similar IOP response to the same PGA. Further studies to understand IOP fluctuation are necessary to improve current methods of assessing medication response.Proprietary or commercial disclosure may be found after the references.

    View details for DOI 10.1016/j.ophtha.2010.02.020

    View details for Web of Science ID 000283264200002

    View details for PubMedID 20619460

    View details for PubMedCentralID PMC2955184

  • Reproducibility of Optic Nerve Head Parameters Measured With Cirrus HD-OCT in Glaucomatous Eyes Chang, R. T., Mwanza, J., Gendy, M. G., Oakley, J. D., Feuer, W. J., Budenz, D. L. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2010
  • Sensitivity and Specificity of Time-Domain versus Spectral-Domain Optical Coherence Tomography in Diagnosing Early to Moderate Glaucoma OPHTHALMOLOGY Chang, R. T., Knight, O. J., Feuer, W. J., Budenz, D. L. 2009; 116 (12): 2294-2299

    Abstract

    To evaluate the sensitivity and specificity of measurements of retinal nerve fiber layer (RNFL) thickness in early to moderate glaucoma using Stratus time-domain and Cirrus spectral-domain optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA).Evaluation of diagnostic test or technology.Fifty-four glaucoma subjects with early to moderate visual field defects and 50 age-matched normal subjects.Three peripapillary RNFL scans of 1 eye of each subject using Stratus and Cirrus OCT.Sensitivity and specificity of average, quadrant, and clock-hour RNFL thickness.The average age+/-standard deviation in the normal and glaucoma groups was 62.9+/-12.7 years (range, 40-84 years) and 67.6+/-11.4 (range, 42-85 years), respectively (P = 0.05). The glaucoma group consisted of 34 early (average mean deviation, -3.20+/-1.22 dB) and 20 moderate (average mean deviation, -8.05+/-1.87 dB) glaucomas. Cirrus OCT sensitivity and specificity for average RNFL abnormal at the 5% level were 83% and 88%, respectively, and at the 1% level were 65% and 100%, respectively. Stratus OCT sensitivity and specificity for average RNFL abnormal at the 5% level were 80% and 94%, respectively, and at the 1% level were 61% and 100%, respectively. For 1 or more abnormal quadrants at the 5% level, the sensitivity and specificity for Cirrus OCT were 98% and 80%, respectively, and at the 1% level were 87% and 92%, respectively. For 1 or more quadrants abnormal at the 5% level, the sensitivity and specificity for Stratus OCT were 96% and 76%, respectively, and at the 1% level were 74% and 94%, respectively. Cirrus OCT sensitivity and specificity using a criterion of 1 or more abnormal clock hours at the 5% level were 100% and 72%, respectively, and at the 1% level were 85% and 94%, respectively. Stratus OCT sensitivity and specificity for 1 or more abnormal clock hours at the 5% level were 98% and 66%, respectively, and at the 1% level were 85% and 90%, respectively.The sensitivity and specificity of various RNFL parameters using the Cirrus OCT for glaucoma with early to moderate visual field defects are excellent and are equivalent to Stratus OCT.

    View details for DOI 10.1016/j.ophtha.2009.06.012

    View details for Web of Science ID 000272579200005

    View details for PubMedID 19800694

  • Comparison of Retinal Nerve Fiber Layer Measurements Using Time Domain and Spectral Domain Optical Coherent Tomography 39th Annual Meeting of the Association-of-University-Professors-of-Ophthalmology Knight, O. J., Chang, R. T., Feuer, W. J., Budenz, D. L. ELSEVIER SCIENCE INC. 2009: 1271–77

    Abstract

    To determine the agreement between peripapillary retinal nerve fiber layer (RNFL) thickness measurements from Stratus time domain optical coherence tomography (OCT) and Cirrus spectral domain OCT (Carl Zeiss Meditec, Dublin, CA) in normal subjects and subjects with glaucoma.Evaluation of diagnostic test or technology.A total of 130 eyes from 130 normal subjects and subjects with glaucoma were analyzed. The subjects were divided into groups by visual field criteria: normal (n = 29), glaucoma suspect (n = 12), mild glaucoma (n = 41), moderate glaucoma (n = 18), and severe glaucoma (n = 30).Peripapillary RNFL thickness was measured with Stratus Fast RNFL and Cirrus 200 x 200 Optic Disc Scan on the same day in 1 eye of each subject to determine agreement. Two operators used the same instruments for all scans.Student paired t testing, Pearson's correlation coefficient, and Bland-Altman analysis of RNFL thickness measurements.The average age of the glaucoma group was significantly more than that of the normal group: 68.3+/-12.3 years versus 55.7+/-12.1 years, respectively. For Stratus OCT, the average RNFL thickness (mean +/- standard deviation) was 99.4+/-13.2 microm, 94.5+/-15.0 microm, 79.0+/-14.5 microm, 62.7+/-10.2 microm, and 51.0+/-8.9 microm for the normal, suspect, mild, moderate, and severe groups, respectively. For Cirrus OCT, the corresponding measurements were 92.0+/-10.8 microm, 88.1+/-13.5 microm, 73.3+/-11.8 microm, 60.9+/-8.3 microm, and 55.3+/-6.6 microm. All Stratus-Cirrus differences were statistically significant by paired t testing (P<0.001) except for the moderate group (P = 0.11). For average RNFL, there was also a highly significant linear relationship between Stratus minus Cirrus difference and RNFL thickness (P<0.001). Bland-Altman plots showed that the systematic difference of Stratus measurements are smaller than Cirrus at thinner RNFL values but larger at thicker RNFL values.RNFL thickness measurements between Stratus OCT and Cirrus OCT cannot be directly compared. Clinicians should be aware that measurements are generally higher with Stratus than with Cirrus except when the RNFL is very thin, as in severe glaucoma. This difference must be taken into account if comparing Stratus measurements with Cirrus measurements.

    View details for DOI 10.1016/j.ophtha.2008.12.032

    View details for Web of Science ID 000267789900007

    View details for PubMedID 19395086

  • Diagnosing glaucoma progression. International ophthalmology clinics Chang, R. T., Budenz, D. L. 2008; 48 (4): 13-28

    View details for DOI 10.1097/IIO.0b013e31818b63f0

    View details for PubMedID 18936634

  • Calibration of fundus images using spectral domain optical coherence tomography OPHTHALMIC SURGERY LASERS & IMAGING Lujan, B. J., Wang, F., Gregori, G., Rosenfeld, P. J., Knighton, R. W., Puliafito, C. A., Danis, R. P., Hubbard, L. D., Chang, R. T., Budenz, D. L., Seider, M. I., Knight, O. 2008; 39 (4): S15-S20

    Abstract

    Measurements performed on fundus images using current software are not accurate. Accurate measurements can be obtained only by calibrating a fundus camera using measurements between fixed retinal landmarks, such as the dimensions of the optic nerve, or by relying on a calibrated model eye provided by a reading center. However, calibrated spectral domain OCT (SD-OCT) could offer a convenient alternative method for the calibration of any fundus image.The ability to measure exact distances on SD-OCT fundus images was tested by measuring the distance between the center of the fovea and the optic nerve. Calibrated SD-OCT scans measuring 6 X 6 X 2 mm centered on the fovea and the optic nerve were analyzed in 50 healthy right eyes. The foveal center was identified using cross-sectional SD-OCT images, and the center of the optic nerve was identified manually. The SD-OCT scans were registered to each other, and the distances between the center of the optic nerve and fovea were calculated. The overlay of these SD-OCT fundus images on photographic fundus images was performed.Any image of the fundus could be calibrated by overlaying the SD-OCT fundus image, and the measurements were consistent with previously defined calibration methods. The mean distance between the center of the fovea and the center of the optic nerve was 4.32 +/-0.32 mm. The line from the center of the optic nerve to the foveal center had a mean declination of 7.67 +/- 3.88 degrees. Mean horizontal displacement and vertical displacement were 4.27 +/- 0.29 mm and 0.58 +/- 0.29 mm, respectively.The overlay of the SD-OCT fundus image provides a convenient method for calibrating any image of the fundus. This approach should provide a uniform standard when comparing images from different devices and from different reading centers.

    View details for Web of Science ID 000258283000003

    View details for PubMedID 18777875

  • New developments in optical coherence tomography for glaucoma CURRENT OPINION IN OPHTHALMOLOGY Chang, R., Budenz, D. L. 2008; 19 (2): 127-135

    Abstract

    Structural imaging is becoming a powerful adjunct for the diagnosis and progression of glaucoma. There are several competing technologies in this arena. Optical coherence tomography continues to evolve at a fast pace, so it can be challenging to keep up with the latest information. This review covers the recent papers relevant to optical coherence tomography for glaucoma.Retinal nerve fiber layer imaging by optical coherence tomography is reliable. Age, ethnicity, axial length and optic disc size can affect the machine's normative range. Scan quality can be affected by movement, media opacities, myopia and severity of disease. The sensitivity and specificity are variable across multiple studies. Despite this, the technology is beginning to help us understand the structure-function relationship in glaucoma.The next generation optical coherence tomography is around the corner. By understanding the current strengths and limitations of this advancing technology, one can better assess its use in clinical practice.

    View details for Web of Science ID 000253545800008

    View details for PubMedID 18301286

  • Reproducibility of retinal nerve fiber thickness measurements using the stratus OCT in normal and glaucomatous eyes Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Budenz, D. L., Chang, R. T., Huang, X. R., Knighton, R. W., Tielsch, J. M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2005: 2440–43

    Abstract

    To determine the reproducibility of Stratus Optical Coherence Tomography (OCT) retinal nerve fiber layer (RNFL) measurements around the optic nerve in normal and glaucomatous eyes.One eye was chosen at random from 88 normal subjects and 59 glaucomatous subjects distributed among mild, moderate, and severe glaucoma, determined by visual field testing. Subjects underwent six RNFL thickness measurements performed by a single operator over a 30-minute period with a brief rest between sessions. Three scans were taken with the high-density Standard RNFL protocol, and three were taken with the Fast RNFL protocol, alternating between scan protocols.Reliability, as measured by intraclass correlation coefficient (ICC), was calculated for the overall mean RNFL thickness and for each quadrant. The ICC for the mean Standard RNFL thickness (and lower 95% confidence interval [CI]) in normal and glaucomatous eyes was 0.97 (0.96 CI) and 0.98 (0.97 CI), respectively. The ICC for the mean Fast RNFL thickness in normal and glaucomatous eyes was 0.95 (0.93 CI) and 0.97 (0.95 CI), respectively. Quadrant ICCs ranged between 0.79 and 0.97, with the nasal quadrant being the least reproducible of all four quadrants, using either the Standard or Fast RNFL program. The test-retest variability ranged from 3.5 microm for the average RNFL thickness measurements in normal eyes to 13.8 microm for the nasal quadrant measurements in glaucomatous eyes, which appeared to be the most variable.Reproducibility of RNFL measurements using the Stratus OCT is excellent in normal and glaucomatous eyes. The nasal quadrant appears to be the most variable measurement. Standard RNFL and Fast RNFL scans are equally reproducible and yield comparable measurements. These findings have implications for the diagnosis of glaucoma and glaucomatous progression.

    View details for DOI 10.1167/iovs.04-1174

    View details for Web of Science ID 000230112800029

    View details for PubMedID 15980233

  • Prospective randomized comparison of 2 different methods of 5% povidone-iodine applications for anterior segment intraocular surgery. Archives of ophthalmology Miño de Kaspar, H., Chang, R. T., Singh, K., Egbert, P. R., Blumenkranz, M. S., Ta, C. N. 2005; 123 (2): 161-165

    Abstract

    To determine the efficacy of reducing conjunctival bacteria flora with 2 different regimens of 5% povidone-iodine application: 2 drops on the conjunctiva cul-de-sac vs a 10-mL conjunctival irrigation of the fornices.In this prospective controlled trial, 200 eyes undergoing anterior segment intraocular surgery were randomized to control and study groups. All patients from both groups received topical ofloxacin and a povidone-iodine scrub of the periorbital area before the surgical procedure. The eyes in the control group received 2 drops of povidone-iodine on the conjunctiva preoperatively, whereas eyes in the study group had irrigation of the fornices with 10 mL of povidone-iodine. Conjunctival cultures were obtained at 4 separate time points before and after surgery.Twenty (26%) of 78 eyes in the study group had positive conjunctival cultures immediately prior to surgery compared with 40 (43%) of 94 eyes in the control group (P = .02). At the conclusion of the surgery, 14 (18%) of 78 eyes and 30 (32%) of 94 eyes had positive cultures in the study and control groups, respectively (P = .05).Irrigation of the fornices with 5% povidone-iodine was associated with significantly fewer positive conjunctival cultures at the time of surgery compared with the application of 2 drops on the conjunctiva.

    View details for PubMedID 15710810

  • Prospective Randomized comparison of 2 different methods of 5% povidone-lodine applications for anterior segment, Intraocular surgery 106th Annual Meeting of the American-Academy-of-Ophthalmology de Kaspar, H. M., Chang, R. T., Singh, K., Egbert, P. R., Blumenkranz, M. S., Ta, C. N. AMER MEDICAL ASSOC. 2005: 161–65

    Abstract

    To determine the efficacy of reducing conjunctival bacteria flora with 2 different regimens of 5% povidone-iodine application: 2 drops on the conjunctiva cul-de-sac vs a 10-mL conjunctival irrigation of the fornices.In this prospective controlled trial, 200 eyes undergoing anterior segment intraocular surgery were randomized to control and study groups. All patients from both groups received topical ofloxacin and a povidone-iodine scrub of the periorbital area before the surgical procedure. The eyes in the control group received 2 drops of povidone-iodine on the conjunctiva preoperatively, whereas eyes in the study group had irrigation of the fornices with 10 mL of povidone-iodine. Conjunctival cultures were obtained at 4 separate time points before and after surgery.Twenty (26%) of 78 eyes in the study group had positive conjunctival cultures immediately prior to surgery compared with 40 (43%) of 94 eyes in the control group (P = .02). At the conclusion of the surgery, 14 (18%) of 78 eyes and 30 (32%) of 94 eyes had positive cultures in the study and control groups, respectively (P = .05).Irrigation of the fornices with 5% povidone-iodine was associated with significantly fewer positive conjunctival cultures at the time of surgery compared with the application of 2 drops on the conjunctiva.

    View details for Web of Science ID 000226755000002

  • Sensitivity and specificity of the StratusOCT for perimetric glaucoma OPHTHALMOLOGY Budenz, D. L., Michael, A., Chang, R. T., McSoley, J., Katz, J. 2005; 112 (1): 3-9

    Abstract

    To determine the sensitivity and specificity of measurements of the retinal nerve fiber layer (RNFL) using the StratusOCT in glaucoma subjects with visual field (VF) defects.Prospective cross-sectional study.One hundred nine normal and 63 glaucoma subjects.Fast RNFL scans were performed in one eye of each patient using the StratusOCT.Sensitivity and specificity of different optical coherence tomography (OCT) criteria for identifying glaucoma subjects with glaucomatous VF defects.Areas under the receiver operating characteristic curves (AROCs) for various OCT parameters.Severity of VF defects in the glaucoma group was distributed between mild (18 subjects), moderate (21 subjects), and severe (24 subjects). The average mean deviation of the glaucoma fields was -8.4 decibels (dB), with a standard deviation of 6.0 dB and a range from -0.14 to -28.0 dB. The sensitivity and specificity using a criterion of average RNFL thickness abnormal at the <5% level were 84% and 98%, respectively. The sensitivity and specificity using a criterion of average RNFL thickness abnormal at the <1% level were 68% and 100%. The sensitivity and specificity of using a criterion of >or=1 quadrants abnormal at the <5% level were 89% and 95%. The sensitivity and specificity of using a criterion of >or=1 quadrants abnormal at the <1% level were 83% and 100%. The sensitivity and specificity of using a criterion of >or=1 clock hours abnormal at the <5% level were 89% and 92%. The sensitivity and specificity of using a criterion of >or=1 quadrants abnormal at the <1% level were 83% and 100%. The AROC for mean RNFL thickness was 0.966. Other high AROC values included the superior quadrant (0.952), inferior quadrant (0.971), inferotemporal clock hour at 7-o'clock (right eye) and 5-o'clock (left eye) (0.959), 6-o'clock hour (0.940), superotemporal clock hour at 11-o'clock (right eye) and 1-o'clock (left eye) (0.935), and 12-o'clock hour (0.924).The sensitivity and specificity of RNFL measurements using the new StratusOCT for glaucoma with manifest VF defects are excellent. The best parameters seem to be >or=1 quadrants abnormal at the or=1 clock hours abnormal at the

    View details for DOI 10.1016/j.ophtha.2004.06.039

    View details for Web of Science ID 000226242800002

    View details for PubMedID 15629813

  • Three-day application of topical ofloxacin reduces the contamination rate of microsurgical knives in cataract surgery - A prospective randomized study Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology de Kaspar, H. M., Chang, R. T., Shriver, E. M., Singh, K., Egbert, P. R., Blumenkranz, M. S., Ta, C. N. ELSEVIER SCIENCE INC. 2004: 1352–55

    Abstract

    To determine the rate of contamination of microsurgical knives during cataract surgery and the benefit of a 3-day versus a 1-hour preoperative application of topical ofloxacin in reducing the contamination rate.Prospective, randomized controlled trial.Seventy-eight eyes of 75 patients were randomly assigned to control (39 eyes) or study groups (39 eyes).All patients from both groups received 0.3% topical ofloxacin 1 hour before surgery, 5% povidone-iodine (PVI) scrub of the periorbital area, and 2 drops of PVI onto the ocular surface preoperatively. The patients in the study group also received ofloxacin 4 times a day for 3 days before surgery.Microsurgical knives were placed in blood culture broth media immediately after the incision had been made. The number of positive cultures and types of bacteria isolated were determined.Ten of 39 knives (26%) in the control group were found to be positive for bacterial growth compared with only 2 of 39 (5%) in the study group (P = 0.028).The initial paracentesis incision frequently results in contamination of the microsurgical knife and may serve as a mechanism for introducing bacteria from the ocular surface into the anterior chamber. The application of topical ofloxacin for 3 days before surgery significantly reduces the contamination rate of the microsurgical knives, compared with a preoperative application of ofloxacin given 1 hour before surgery.

    View details for PubMedID 15234136

  • Antibiotic resistance patterns of ocular bacterial flora - A prospective study of patients undergoing anterior segment surgery Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Ta, C. N., Chang, R. T., Singh, K., Egbert, P. R., Shriver, E. M., Blumenkranz, M. S., de Kaspar, H. M. ELSEVIER SCIENCE INC. 2003: 1946–51

    Abstract

    To determine the antibiotic susceptibility patterns of conjunctival bacterial flora isolated preoperatively from patients undergoing anterior segment surgery.Prospective observational study.One hundred fifty-six eyes from 139 patients scheduled for anterior segment surgery were enrolled over a 6-month period from August 2001 to February 2002.Conjunctival cultures were obtained on the day of surgery before povidone-iodine or antibiotic application.Bacterial isolates were identified and tested for antibiotic susceptibility using the Kirby-Bauer disc-diffusion technique.Among the 156 eyes studied, 36 were from patients who had undergone either bilateral surgery or more than one surgery in the same eye. Only the first eyes of the 120 patients that underwent initial ocular surgery were included in our analysis. Of these 120 eyes, 21 (18%) showed no bacterial growth. Of the 143 bacterial strains isolated from the remaining 99 eyes, 112 (78%) were coagulase-negative staphylococci (CNS). Among the CNS, greater than 90% were susceptible to cefotaxime, levofloxacin, imipenem, meropenem, vancomycin, and each of the aminoglycosides except neomycin. Between 70% and 90% of the CNS were susceptible to cefazolin, neomycin, ciprofloxacin, ofloxacin, norfloxacin, and chloramphenicol. Less than 70% of the isolated CNS were sensitive to the penicillin analogues, ceftazidime, erythromycin, and tetracycline.Preoperative conjunctival isolates of CNS seem to be most sensitive to vancomycin, the aminoglycosides (except neomycin), and levofloxacin.

    View details for DOI 10.1016/S0161-6420(03)00735-8

    View details for PubMedID 14522770

  • Bacterial contamination of paracentesis blades used in cataract surgery Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Chang, R. T., Ta, C. N., Egbert, P. R., Singh, K., Haw, W. W., Shriver, E. M., Espinosa, L., Williams, D. Y., Blumenkranz, M. S., de Kaspar, H. M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U73–U73
  • Role of topical ciprofloxacin and 5%-povidone-iodine prior to cataract surgery: a randomized study in Paraguay Froehlich, S. J., Samudio, M., Laspina, F., Carron, J., Klauss, Chang, R., de Kasper, H. M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U349
  • Antibiotic susceptibility pattern of coagulase-negative staphylococci in patients undergoing Intraocular surgery Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Ta, C. N., de Kaspar, H. M., Chang, R. T., Shriver, E. M., Egbert, P. R., Singh, K., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U1275–U1275
  • Multiresistant Staphylococcus epidermidis on the conjunctiva prior to intraocular surgery Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Shriver, E. M., Ta, C. N., Egbert, P. R., Singh, K., Chang, R. T., Blumenkranz, M. S., de Kaspar, H. M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U860–U860
  • Glaucoma Suspect: Diagnosis and Management. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) Chang, R. T., Singh, K. n. ; 5 (1): 32–37

    Abstract

    Glaucoma suspect is a diagnosis reserved for individuals who do not definitively have glaucoma at the present time but have characteristics suggesting that they are at high risk of developing the disease in the future based on a variety of factors. This review provides a practical approach to individuals classified as glaucoma suspects caused by one or more of the following risk factors or indicators of disease: ocular hypertension, optic nerve features suggestive of glaucoma, visual field abnormalities, and other characteristics placing them at greater risk than the average population. In addition to diagnostic considerations, this overview provides information on therapeutic approaches to the glaucoma suspect.

    View details for PubMedID 26886117

  • Update on the Medical Treatment of Primary Open-Angle Glaucoma. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) Cheema, A. n., Chang, R. T., Shrivastava, A. n., Singh, K. n. ; 5 (1): 51–58

    Abstract

    Glaucoma comprises a group of progressive, neurodegenerative disorders characterized by retinal ganglion cell death and nerve fiber layer atrophy. Several randomized controlled trials have consistently demonstrated the efficacy of intraocular pressure lowering to slow or halt the measurable progression of the disease. Medical therapy, in places where it is easily accessible, is often the primary method to lower intraocular pressure. We review the medical options currently available and possible future options currently in development. The 5 contemporary classes of topical agents in use include prostaglandin analogs, beta blockers, carbonic anhydrase inhibitors, alpha agonists, and cholinergics. In addition, several fixed combination agents are commercially available. Agents from each of these classes have unique mechanisms of action, adverse effects, and other characteristics that impact how they are used in clinical practice. Despite the plethora of medical options available, there are limitations to topical ophthalmic therapy such as the high rate of noncompliance and local and systemic adverse effects. Alternate and sustained drug delivery models, such as injectable agents and punctal plug delivery systems, may in the future alleviate some such concerns and lead to increased efficacy of treatment while minimizing adverse effects.

    View details for PubMedID 26886120