David Myung, MD, PhD

All Publications

• 3D Printable, Modified Trephine Designs for Consistent Anterior Lamellar Keratectomy Wounds in Rabbits. Current eye research Chen, F., Buickians, D., Le, P., Xia, X., Montague-Alamin, S. Q., Blanco Varela, I. B., Mundy, D. C., Logan, C. M., Myung, D. 2021: 1?10

  Abstract

  Purpose: Our goal is to develop a low-cost tool that can be used to create consistent, partial-thickness defects in rabbit and other large animals with minimal surgical training and that can facilitate pre-clinical testing of lamellar and in situ-forming biosynthetic matrix materials for corneal repair. Materials & Methods: In this study, three modified trephines were designed to create deep corneal wound defects with consistent depth in large animals. The modified trephines incorporated either 3D-printed parts made from photopolymerizable resins, or custom-cut commercially available Teflon sheets. Wound defects were imaged with optical coherence tomography (OCT), and the depth was analyzed based on the OCT images. Results: The results revealed that an inner-stopper guard trephine had the best performance in creating consistent and precise wound defect depth compared to modified vacuum trephine and custom guard vacuum trephine. A 75% ± 10% cut of the cornea was achieved with the inner-stopper guard trephine. The wound defect depth by created by the inner-stopper guard trephine was independent of the corneal thickness or size of the globes. Although the cut depth of the inner-stopper guard trephine differed by the experience-level of its users, the consistency (standard deviation) of the depth was independent of experience. Conclusions: Our studies provided three cost-efficient animal trephines that can create corneal wounds of consistent depth by lab researchers without extensive training in keratectomy.

  View details for DOI 10.1080/02713683.2020.1868010

  View details for PubMedID 33474996

• A deep learning approach to identify blepharoptosis by convolutional neural networks. International journal of medical informatics Hung, J. Y., Perera, C., Chen, K. W., Myung, D., Chiu, H. K., Fuh, C. S., Hsu, C. R., Liao, S. L., Kossler, A. L. 2021; 148: 104402

  Abstract

  Blepharoptosis is a known cause of reversible vision loss. Accurate assessment can be difficult, especially amongst non-specialists. Existing automated techniques disrupt clinical workflow by requiring user input, or placement of reference markers. Neural networks are known to be effective in image classification tasks. We aim to develop an algorithm that can accurately identify blepharoptosis from a clinical photo.A total of 500 clinical photographs from patients with and without blepharoptosis were sourced from a tertiary ophthalmic center in Taiwan. Images were labeled by two oculoplastic surgeons, with an independent third oculoplastic surgeon to adjudicate disagreements. These images were used to train a series of convolutional neural networks (CNNs) to ascertain the best CNN architecture for this particular task.Of the models that trained on the dataset, most were able to identify ptosis images with reasonable accuracy. We found the best performing model to use the DenseNet121 architecture without pre-training which achieved a sensitivity of 90.1 % with a specificity of 82.4 %, compared to the worst performing model which was used a Resnet34 architecture with pre-training, achieving a sensitivity of 74.1 %, and specificity of 63.6 %. Models with and without pre-training performed similarly (mean accuracy 82.6 % vs. 85.8 % respectively, p = 0.06), though models with pre-training took less time to train (1-minute vs. 16 min, p < 0.01).We report the use of AI to accurately diagnose blepharoptosis from a clinical photograph with no external reference markers or user input requirement. Most current-generation CNN architectures performed reasonably on this task, with the DenseNet121, and Resnet18 architectures without pre-training performing best in our dataset.

  View details for DOI 10.1016/j.ijmedinf.2021.104402

  View details for PubMedID 33609928

• 3D Bioprinting using UNIversal Orthogonal Network (UNION) Bioinks. Advanced functional materials Hull, S. M., Lindsay, C. D., Brunel, L. G., Shiwarski, D. J., Tashman, J. W., Roth, J. G., Myung, D., Feinberg, A. W., Heilshorn, S. C. 2021; 31 (7)

  Abstract

  Three-dimensional (3D) bioprinting is a promising technology to produce tissue-like structures, but a lack of diversity in bioinks is a major limitation. Ideally each cell type would be printed in its own customizable bioink. To fulfill this need for a universally applicable bioink strategy, we developed a versatile, bioorthogonal bioink crosslinking mechanism that is cell compatible and works with a range of polymers. We term this family of materials UNIversal, Orthogonal Network (UNION) bioinks. As demonstration of UNION bioink versatility, gelatin, hyaluronic acid (HA), recombinant elastin-like protein (ELP), and polyethylene glycol (PEG) were each used as backbone polymers to create inks with storage moduli spanning 200 to 10,000 Pa. Because UNION bioinks are crosslinked by a common chemistry, multiple materials can be printed together to form a unified, cohesive structure. This approach is compatible with any support bath that enables diffusion of UNION crosslinkers. Both matrix-adherent human corneal mesenchymal stromal cells and non-matrix-adherent human induced pluripotent stem cell-derived neural progenitor spheroids were printed with UNION bioinks. The cells retained high viability and expressed characteristic phenotypic markers after printing. Thus, UNION bioinks are a versatile strategy to expand the toolkit of customizable materials available for 3D bioprinting.

  View details for DOI 10.1002/adfm.202007983

  View details for PubMedID 33613150

  View details for PubMedCentralID PMC7888563

• 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

• Management of acute corneal hydrops with intracameral gas injection. American journal of ophthalmology case reports Sayadi, J. J., Lam, H., Lin, C. C., Myung, D. 2020; 20: 100994

  Abstract

  Purpose: To report two cases of severe acute corneal hydrops that were resolved by intracameral gas injection alone.Observations: Case 1 is a 27-year-old woman with bilateral severe keratoconus who developed sequential acute corneal hydrops in the right eye followed by the left eye that were each successfully treated using intracameral 20% sulfur hexafluoride gas injection. Case 2 is a 62-year-old man that developed a large fluid cleft beneath a pre-existing LASIK flap, which resolved with intracameral 20% sulfur hexafluoride gas injection without the need for corneal transplantation.Conclusions and importance: In acute corneal hydrops, intracameral gas injection to tamponade Descemet's membrane tears with decompression of stromal fluid can be an effective intervention to delay or avoid keratoplasty in individuals whose corneal hydrops does not improve with conventional medical management.

  View details for DOI 10.1016/j.ajoc.2020.100994

  View details for PubMedID 33319122

• 3D Bioprinting using UNIversal Orthogonal Network (UNION) Bioinks ADVANCED FUNCTIONAL MATERIALS Hull, S. M., Lindsay, C. D., Brunel, L. G., Shiwarski, D. J., Tashman, J. W., Roth, J. G., Myung, D., Feinberg, A. W., Heilshorn, S. C. 2020

  View details for DOI 10.1002/adfm.202007983

  View details for Web of Science ID 000590660600001

• Development, Validation, and Innovation in Ophthalmic Laser-Based Imaging: Report From a US Food and Drug Administration-Cosponsored Forum. JAMA ophthalmology Brodie, F., Repka, M., Burns, S. A., Prakalapakorn, S. G., Morse, C., Schuman, J. S., Duenas, M. R., Afshari, N., Pollack, J. S., Thorne, J. E., Vitale, A., Sen, H. N., Myung, D., Blumenkranz, M. S., Tu, E., Hammer, D. X., Tarver, M., Cunningham, B., Kagemann, L., Sadda, S., Sarraf, D., Jaffe, G. J., Eydelman, M. 2020

  Abstract

  In April 2019, the US Food and Drug Administration, in conjunction with 11 professional ophthalmic, vision science, and optometric societies, convened a forum on laser-based imaging. The forum brought together the Food and Drug Administration, clinicians, researchers, industry members, and other stakeholders to stimulate innovation and ensure that patients in the US are the first in the world to have access to high-quality, safe, and effective medical devices. This conference focused on the technology, clinical applications, regulatory issues, and reimbursement issues surrounding innovative ocular imaging modalities. Furthermore, the emerging role of artificial intelligence in ophthalmic imaging was reviewed. This article summarizes the presentations, discussion, and future directions.

  View details for DOI 10.1001/jamaophthalmol.2020.4994

  View details for PubMedID 33211074

• Gold nanoparticles to enhance ophthalmic imaging. Biomaterials science Chen, F., Si, P., de la Zerda, A., Jokerst, J. V., Myung, D. 2020

  Abstract

  The use of gold nanoparticles as diagnostic tools is burgeoning, especially in the cancer community with a focus on theranostic applications to both cancer diagnosis and treatment. Gold nanoparticles have also demonstrated great potential for use in diagnostic and therapeutic approaches in ophthalmology. Although many ophthalmic imaging modalities are available, there is still a considerable unmet need, in particular for ophthalmic molecular imaging for the early detection of eye disease before morphological changes are more grossly visible. An understanding of how gold nanoparticles are leveraged in other fields could inform new ways they could be utilized in ophthalmology. In this paper, we review current ophthalmic imaging techniques and then identify optical coherence tomography (OCT) and photoacoustic imaging (PAI) as the most promising technologies amenable to the use of gold nanoparticles for molecular imaging. Within this context, the development of gold nanoparticles as OCT and PAI contrast agents are reviewed, with the most recent developments described in detail.

  View details for DOI 10.1039/d0bm01063d

  View details for PubMedID 33057463

• Simultaneous Interpenetrating Polymer Network of Collagen and Hyaluronic Acid as an In Situ-Forming Corneal Defect Filler CHEMISTRY OF MATERIALS Chen, F., Le, P., Lai, K., Fernandes-Cunha, G. M., Myung, D. 2020; 32 (12): 5208?16

  View details for DOI 10.1021/acs.chemmater.0c01307

  View details for Web of Science ID 000543738500033

• Bioengineered, In Situ-Crosslinked Collagen Gels for Suture-Free Stromal Defect Reconstruction of the Cornea Myung, D., Djalilian, A. R., Heilshorn, S., Chen, F., Le, P., Hull, S., Fernandes-Cunha, G., Na, K. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554528301263

• Optimization of an in situ-forming interpenetrating polymer network of collagen and hyaluronic acid hydrogel independently and simultaneously crosslinked by click chemistries Le, P., Chen, F., Cunha, G., Lai, K., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554495700138

• Design and development of a novel electroretinogram-microperimetry system with superimposed multifocal arrays Suzuki, N., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554495701225

• In situ-forming bio-orthogonally crosslinked collagen-hyaluronate co-polymeric hydrogel to treat deep corneal stromal defects: in vivo biological response Chen, F., Le, P., Cunha, G., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554495702200

• Supramolecular guest-host hyaluronic acid hydrogels for epithelial cell delivery to the cornea Chen, K., Cunha, G., Jung, S., Hahn, S., Lee, G., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554495700275

• Encapsulation of Corneal Stromal Stem Cells within Supramolecular Host-Guest Hyaluronic Acid Gels Seo, Y., Chen, K., Fernandes-Cunha, G., Jung, S., Lee, G., Hahn, S., Djalilian, A. R., Jabbehdari, S., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554495700132

• Assessment of Eye Disease and Visual Impairment in the Nursing Home Population Using Mobile Health Technology OPHTHALMIC SURGERY LASERS & IMAGING RETINA Lai, K. Y., Pathipati, M. P., Blumenkranz, M. S., Leung, L., Moshfeghi, D. M., Toy, B. C., Myung, D. 2020; 51 (5): 262?70

  Abstract

  To characterize the burden of eye disease and the utility of teleophthalmology in nursing home patients, a population with ophthalmic needs not commensurate with care received.Informed consent was obtained from 78 California Bay Area skilled nursing facility patients. Near visual acuity (VA) and anterior/posterior segment photographs were taken with a smartphone-based VA app and ophthalmic camera system. The Nursing Home Vision-Targeted Health-Related Quality of Life questionnaire was also administered. Risk factors for visual impairment were assessed. Institutional review board approval was obtained from Stanford University.Cataracts (51%), diabetic retinopathy (DR) (12%), optic neuropathy (12%), and age-related macular degeneration (AMD) (10%) were common findings; 11.7% had other referral-warranted findings. AMD and DR correlated with a higher risk of poor VA, with adjusted odds ratios of 22 (P = .01) and 43 (P = .004).This study demonstrated a high prevalence of poor VA and ophthalmic disease in the nursing home population impacting quality of life. Smartphone-based teleophthalmology platforms have the potential to increase access to eye care for nursing home patients. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:262-270.].

  View details for DOI 10.3928/23258160-20200501-03

  View details for Web of Science ID 000539315500003

  View details for PubMedID 32511729

• Injectable Cucurbit[8]uril-Based Supramolecular Gelatin Hydrogels for Cell Encapsulation ACS MACRO LETTERS Madl, A. C., Madl, C. M., Myung, D. 2020; 9 (4): 619?26

  View details for DOI 10.1021/acsmacrolett.0c00184

  View details for Web of Science ID 000527769900029

• Utility and Feasibility of Teleophthalmology Using a Smartphone-Based Ophthalmic Camera in Screening Camps in Nepal. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) Collon, S., Chang, D., Tabin, G., Hong, K., Myung, D., Thapa, S. ; 9 (1): 54?58

  Abstract

  To determine whether use of a mobile device-based ophthalmic camera by ophthalmic technicians (OTs) in village screening camps in Nepal followed by remote image interpretation by an ophthalmologist can improve detection of ocular pathology and medical decision-making.Evaluation of mobile device-based ophthalmic camera through study of before and after clinical decision-making.One hundred forty patients over 18 years of age presenting to remote screening camps with best-corrected visual acuity ?20/60 in one or both eyes were enrolled. Participants were examined by an OT with direct ophthalmoscopy. The technician recorded a diagnosis for each eye and a disposition for each patient. Patients then had anterior segment and fundus photos and/or videos taken using a smartphone-based ophthalmic camera system. Photos and videos were uploaded to a secure, HIPAA-compliant, cloud-based server, and interpreted by masked ophthalmologists from XXX, who independently recorded diagnoses and a disposition for each patient.The diagnoses given by OTs and ophthalmologists differed in 42.4% of eyes. Diagnosis agreement was highest for cataract [k?=?0.732, 95% confidence interval (CI) 0.65-0.81], but much lower for posterior segment (retina/optic nerve) pathology (k?=?0.057, 95% CI -0.03-0.14). Ophthalmologists and OTs suggested different dispositions for 68.6% of patients. Agreement was highest for cataract extraction (k?=?0.623, 95% CI 0.49-0.75), whereas agreement for referral to XXX was lower (k?=?0.12, 95% CI 0.00-0.24).Remote ophthalmologist consultation utilizing a mobile device ophthalmic camera system is logistically feasible, easily scalable, and capable of capturing high-quality images in the setting of rural eye screening camps. Although OTs are well equipped to identify and triage anterior segment pathology, this technology may be helpful in the detection of and referral for posterior segment pathology.

  View details for DOI 10.1097/01.APO.0000617936.16124.ba

  View details for PubMedID 31990747

• Wireless smart contact lens for diabetic diagnosis and therapy SCIENCE ADVANCES Keum, D., Kim, S., Koo, J., Lee, G., Jeon, C., Mok, J., Mun, B., Lee, K., Kamrani, E., Joo, C., Shin, S., Sim, J., Myung, D., Yun, S., Bao, Z., Hahn, S. 2020; 6 (17): eaba3252

  Abstract

  A smart contact lens can be used as an excellent interface between the human body and an electronic device for wearable healthcare applications. Despite wide investigations of smart contact lenses for diagnostic applications, there has been no report on electrically controlled drug delivery in combination with real-time biometric analysis. Here, we developed smart contact lenses for both continuous glucose monitoring and treatment of diabetic retinopathy. The smart contact lens device, built on a biocompatible polymer, contains ultrathin, flexible electrical circuits and a microcontroller chip for real-time electrochemical biosensing, on-demand controlled drug delivery, wireless power management, and data communication. In diabetic rabbit models, we could measure tear glucose levels to be validated by the conventional invasive blood glucose tests and trigger drugs to be released from reservoirs for treating diabetic retinopathy. Together, we successfully demonstrated the feasibility of smart contact lenses for noninvasive and continuous diabetic diagnosis and diabetic retinopathy therapy.

  View details for DOI 10.1126/sciadv.aba3252

  View details for Web of Science ID 000530628100044

  View details for PubMedID 32426469

  View details for PubMedCentralID PMC7182412

• Multifunctional materials for implantable and wearable photonic healthcare devices NATURE REVIEWS MATERIALS Lee, G., Moon, H., Kim, H., Lee, G., Kwon, W., Yoo, S., Myung, D., Yun, S., Bao, Z., Hahn, S. 2020

  View details for DOI 10.1038/s41578-019-0167-3

  View details for Web of Science ID 000508153800001

• Microsurgical Resection of an Orbital Arteriovenous Malformation With Intraoperative Digital Subtraction Angiography. Ophthalmic plastic and reconstructive surgery Rosenblatt, T. R., Myung, D., Fischbein, N. J., Steinberg, G. K., Kossler, A. L. 2020

  View details for DOI 10.1097/IOP.0000000000001815

  View details for PubMedID 32976328

• Simultaneous Interpenetrating Polymer Network of Collagen and Hyaluronic Acid as an In Situ-Forming Corneal Defect Filler. Chemistry of materials : a publication of the American Chemical Society Chen, F., Le, P., Lai, K., Fernandes-Cunha, G. M., Myung, D. 2020; 32 (12): 5208?16

  Abstract

  Timely treatment of corneal injuries injury can help to prevent corneal scarring, blindness, and the need for corneal transplantation. This work describes a novel hydrogel that can fill corneal defects and assist in corneal regeneration. This hydrogel is a simultaneous interpenetrating polymer network (IPN) composed of collagen cross-linked via strain-promoted azide-alkyne cycloaddition reaction and hyaluronic acid cross-linked via thiol-ene Michael click reaction. The formation of the IPN gel was confirmed via FTIR spectra, UV-vis spectra, and morphological changes. We compared the gelation time, mechanical properties, transmittance, and refractive index of the IPN gel to the collagen gel, hyaluronic acid gel, and semi-IPN gel. The IPN combined the advantages of collagen and hyaluronic acid gels and supported corneal epithelial cell growth on its surface. When applied to corneal stromal defects in vivo, the IPN avoided epithelial hyperplasia, decreased stromal myofibroblast formation, and increased tight junction formation in the regenerated epithelium.

  View details for DOI 10.1021/acs.chemmater.0c01307

  View details for PubMedID 33603277

  View details for PubMedCentralID PMC7888987

• In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects. Scientific reports Fernandes-Cunha, G. M., Chen, K. M., Chen, F., Le, P., Han, J. H., Mahajan, L. A., Lee, H. J., Na, K. S., Myung, D. 2020; 10 (1): 16671

  Abstract

  Visually significant corneal injuries and subsequent scarring collectively represent a major global human health challenge, affecting millions of people worldwide. Unfortunately, less than 2% of patients who could benefit from a sight-restoring corneal transplant have access to cadaveric donor corneal tissue. Thus, there is a critical need for new ways to repair corneal defects that drive proper epithelialization and stromal remodeling of the wounded area without the need for cadeveric donor corneas. Emerging therapies to replace the need for donor corneas include pre-formed biosynthetic buttons and in situ-forming matrices that strive to achieve the transparency, biocompatibility, patient comfort, and biointegration that is possible with native tissue. Herein, we report on the development of an in situ-forming hydrogel of collagen type I crosslinked via multi-functional polyethylene glycol (PEG)-N-hydroxysuccinimide (NHS) and characterize its biophysical properties and regenerative capacity both in vitro and in vivo. The hydrogels form under ambient conditions within minutes upon mixing without the need for an external catalyst or trigger such as light or heat, and their transparency, degradability, and stiffness are modulated as a function of number of PEG arms and concentration of PEG. In addition, in situ-forming PEG-collagen hydrogels support the migration and proliferation of corneal epithelial and stromal cells on their surface. In vivo studies in which the hydrogels were formed in situ over stromal keratectomy wounds without sutures showed that they supported multi-layered surface epithelialization. Overall, the in situ forming PEG-collagen hydrogels exhibited physical and biological properties desirable for a corneal stromal defect wound repair matrix that could be applied without the need for sutures or an external trigger such as a catalyst or light energy.

  View details for DOI 10.1038/s41598-020-72978-5

  View details for PubMedID 33028837

• 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., Chang, R. T., Myung, D., Onyango, J. 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

• Bio-orthogonally crosslinked hyaluronate-collagen hydrogel for suture-free corneal defect repair. Biomaterials Chen, F., Le, P., Fernandes-Cunha, G. M., Heilshorn, S. C., Myung, D. 2020; 255: 120176

  Abstract

  Biomaterials that mimic corneal stroma could decrease the need for donor corneal tissue and could decrease the prevalence of complications associated with corneal transplantation, including infection and rejection. We developed a bio-orthogonally crosslinked hyaluronate-collagen hydrogel which can fill corneal defects in situ without the need for any sutures, initiators, or catalysts. We studied the effects of biorthogonal crosslinking on the light transmittance of the hydrogel, which was greater than 97% water. The transmittance of the optimized hydrogel in the visible light range was over 94%. We also investigated the mechanical properties, refractive index, morphology, biocompatibility, and corneal re-epithelialization capacity of the hyaluronate-collagen hydrogel. Our in vitro, in vivo, and ex vivo results demonstrated that this bio-orthogonally crosslinked hyaluronate-collagen hydrogel has excellent potential as a biomaterial for cornea repair and regeneration.

  View details for DOI 10.1016/j.biomaterials.2020.120176

  View details for PubMedID 32559566

• Engineering an electrospun nanofiber to direct corneal epithelial cell proliferation and morphology Vo, C., Lee, H., Fernandes-Cunha, G., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488628102086

• An engineered dimeric fragment of hepatocyte growth factor improves corneal epithelial wound healing in vitro Carter, K., Ye, A., Fernandes-Cunha, G., Cochran, J. R., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488628107322

• A novel device for secondary intraocular lens placement: Design and Ex Vivo Evaluation Buickians, D., Myung, D., Blumenkranz, M. S., Brodie, F. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488628101085

• Enhanced wound healing effects of secretome derived from human mesenchymal stem cells cultured on electrospun fibers Myung, D., Fernandes-Cunha, G., Lee, H., Djalilian, A. R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800703177

• Biophysical characterization of a simultaneous interpenetrating polymer network composed of crosslinked collagen and hyaluronic acid Lai, K., Lee, H., Hull, S., Fernandes-Cunha, G., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800701274

• Effects of mesenchymal stem cells encapsulated within crosslinked collagen carrier gels on alkali burns in a corneal organ culture model Blanco, I., Fernandes-Cunha, G., Hull, S., Lee, H., Na, K., Djalilian, A. R., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800703038

• Nonmydriatric Photographic Screening for Diabetic Retinopathy in Pregnant Patients with Pre-existing Diabetes in a County Population Veerappan, M., Myung, D., Jelks, A., Pan, C. K. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800705014

• Characterization of bioorthogonally crosslinked collagen gels with encapsulated corneal stromal stem cells Hull, S., Fernandes-Cunha, G., Putra, I., Eslani, M., Djalilian, A. R., Heilshorn, S., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800701286

• Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier STEM CELLS TRANSLATIONAL MEDICINE Fernandes-Cunha, G., Na, K., Putra, I., Lee, H., Hull, S., Cheng, Y., Blanco, I., Eslani, M., Djalilian, A. R., Myung, D. 2019; 8 (5): 478?89

  View details for DOI 10.1002/sctm.18-0178

  View details for Web of Science ID 000465337000008

• Evaluating New Ophthalmic Digital Devices for Safety and Effectiveness in the Context of Rapid Technological Development. JAMA ophthalmology Bodnar, Z. M., Schuchard, R., Myung, D., Tarver, M. E., Blumenkranz, M. S., Afshari, N. A., Humayun, M. S., Morse, C., Nischal, K., Repka, M. X., Sprunger, D., Trese, M., Eydelman, M. B. 2019

  Abstract

  The US Food and Drug Administration's medical device regulatory pathway was initially conceived with hardware devices in mind. The emerging market for ophthalmic digital devices necessitates an evolution of this paradigm.To facilitate innovation in ophthalmic digital health with attention to safety and effectiveness.This article presents a summary of the presentations, discussions, and literature review that occurred during a joint Ophthalmic Digital Health workshop of the American Academy of Ophthalmology, the American Academy of Pediatrics, the American Association for Pediatric Ophthalmology and Strabismus, the American Society of Cataract and Refractive Surgery, the American Society of Retina Specialists, the Byers Eye Institute at Stanford and the US Food and Drug Administration.Criterion standards and expert graders are critically important in the evaluation of automated systems and telemedicine platforms. Training at all levels is important for the safe and effective operation of digital health devices. The risks associated with automation are substantially increased in rapidly progressive diseases. Cybersecurity and patient privacy warrant meticulous attention.With appropriate attention to safety and effectiveness, digital health technology could improve screening and treatment of ophthalmic diseases and improve access to care.

  View details for DOI 10.1001/jamaophthalmol.2019.1576

  View details for PubMedID 31169870

• Characterizing the impact of 2D and 3D culture conditions on the therapeutic effects of human mesenchymal stem cell secretome on corneal wound healing in vitro and ex vivo. Acta biomaterialia Carter, K., Lee, H. J., Na, K. S., Fernandes-Cunha, G. M., Blanco, I. J., Djalilian, A., Myung, D. 2019

  Abstract

  The therapeutic effects of secreted factors (secretome) produced by bone marrow-derived human mesenchymal stem cells (MSCs) were evaluated as a function of their growth in 2D culture conditions and on 3D electrospun fiber scaffolds. Electrospun fiber scaffolds composed of polycaprolactone and gelatin were fabricated to provide a 3D microenvironment for MSCs, and their mechanical properties were optimized to be similar to corneal tissue. The secretome produced by the MSCs cultured on 3D fiber matrices versus 2D culture dishes were analyzed by Luminex immunoassay, and the secretome of MSCs cultured on the 3D versus 2D substrates showed substantial compositional differences. Concentrations of factors such as HGF and ICAM-1 were increased over 5 times in 3D cultures compared to 2D cultures. In vitro proliferation and scratch-based wound healing assays were performed to compare the effects of the secretome on corneal fibroblast cells (CFCs) when delivered synchronously from co-cultured MSCs through a trans-well co-culture system versus asynchronously after harvesting the factors separately and adding them to the media. Cell viability of CFCs was sustained for 6 days when co-cultured with MSCs seeded on the fibers but decreased with time under other conditions. Scratch assays showed 95% closure at 48 hr when CFCs were co-cultured with MSCs seeded on fibers, while the control group only exhibited 50% closure at 48 hr. Electrospun fibers seeded with MSCs were then applied to a wounded rabbit corneal organ culture system, and MSCs seeded on fibers promoted faster epithelialization and less scarring. Corneas were fixed and stained for alpha smooth muscle actin (?-SMA), and then analyzed by confocal microscopy. Immunostaining showed that expression of alpha-SMA was lower in corneas treated with MSCs seeded on fibers, suggesting suppression of myofibroblastic transformation. MSCs cultured on electrospun fibers facilitate wound healing in CFCs and on explanted corneas through differential secretome profiles compared to MSCs cultured on 2D substrates. Future work is merited to further understand the nature and basis of these differences and their effects in animal models. Statement of Significance: Previous studies have shown that the secretome of bone marrow-derived mesenchymal stem cells (MSC) is beneficial to corneal wound healing by facilitating improved wound closure rates and reduction of scarring and neovascularization. The present research is significant because it provides evidence for the modulation of the secretome as a function of the MSC culture environment. This leads to differential expression of therapeutic factors secreted, which can impact corneal epithelial and stromal healing after severe injury. In addition, this article shows that the co-continuous delivery of the MSC secretome improves cell migration and proliferation over aliquoted delivery, and that MSCs grown on three-dimensional electrospun fiber constructs may provide a favorable microenvironment for cultured MSCs and as a carrier to deliver their secreted factors to the ocular surface.

  View details for DOI 10.1016/j.actbio.2019.09.022

  View details for PubMedID 31539656

• Teleophthalmology through handheld mobile devices: a pilot study in rural Nepal. Journal of mobile technology in medicine Hong, K., Collon, S., Chang, D., Thakalli, S., Welling, J., Oliva, M., Peralta, E., Gurung, R., Ruit, S., Tabin, G., Myung, D., Thapa, S. 2019; 8 (1)

  Abstract

  To compare screening referral recommendations made by remotely located ophthalmic technicians with those of an ophthalmologist examining digital photos obtained by a portable ophthalmic camera system powered by an iOS handheld mobile device (iPod Touch).Dilated screening eye exams were performed by ophthalmic technicians in four remote districts of Nepal. Anterior and posterior segment photographs captured with a Paxos Scope ophthalmic camera system attached to an iPod Touch 6th generation device were uploaded to a secure cloud database for review by an ophthalmologist in Kathmandu. The ophthalmic technicians' referral decisions based on slit-lamp exam were compared to the ophthalmologist's recommendation based on the transmitted images.Using the transmitted images, the ophthalmologist recommended referral for an additional 20% of the 346 total subjects screened who would not have been referred by the ophthalmic technician. Of those subjects, 34% were referred to the retina clinic. Conversely, among the 101 patients referred by the technician, the ophthalmologist concurred with the appropriateness of referral in more than 97% of cases but thought eight (2.8%) of those patients had variants of normal eye pathology.An ophthalmologist who reviewed data and photos gathered with the mobile device teleophthalmology system identified a significant number of patients whose need for referral was not identified by the screening technician. Posterior segment pathology was most frequently found by the remote reader and not by the technician performing dilated slit lamp examinations. These results are promising for further clinical implementation of handheld mobile devices as tools for teleophthalmic screening in resource-limited settings.

  View details for DOI 10.7309/jmtm.8.1.1

  View details for PubMedID 32728400

  View details for PubMedCentralID PMC7388679

• Bio-Orthogonally Crosslinked, In Situ Forming Corneal Stromal Tissue Substitute ADVANCED HEALTHCARE MATERIALS Lee, H., Fernandes-Cunha, G. M., Na, K., Hull, S. M., Myung, D. 2018; 7 (19)

  View details for DOI 10.1002/adhm.201800560

  View details for Web of Science ID 000446822600013

• In situ-forming hyaluronic acid hydrogel through visible light-induced thiolene reaction REACTIVE & FUNCTIONAL POLYMERS Lee, H., Fernandes-Cunha, G. M., Myung, D. 2018; 131: 29?35

  View details for DOI 10.1016/j.reactfunctpolym.2018.06.010

  View details for Web of Science ID 000448225200004

• Mechanical properties of collagen gels crosslinked by copper-free click chemistry and their effects on encapsulated keratocytes Lee, H., Fernandes-Cunha, G., Heilshorn, S., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912506258

• Suppression of alkali burn-induced corneal injury by mesenchymal stem cells encapsulated within crosslinked collagen gels Na, K., Cunha, G., Lee, H., Djalilian, A. R., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442932803217

• Synergistic corneal wound healing effects of human mesenchymal stem cell secreted factors and hyaluronic acid-based viscoelastic gel Rogers, G., Putra, I., Lee, H., Cheng, Y., Eslani, M., Djalilian, A. R., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912509017

• Effects of engineered cellular microenvironments on the secretome of human mesenchymal stem cells Hull, S., Fernandes-Cunha, G., Lee, H., Heilshorn, S., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912506282

• In situ-forming hyaluronic acid hydrogel through visible light-induced thiol-ene reaction. Reactive & functional polymers Lee, H. J., Fernandes-Cunha, G. M., Myung, D. 2018; 131: 29?35

  Abstract

  Here we present hyaluronic acid (HA) hydrogels crosslinked via thiol-ene reaction initiated by visible blue light exposure in the presence of riboflavin phosphate (RFP). The gelation procedure is rapid and proceeds as effectively with exposure to blue light as it does with UV light. We successfully initiated the thiol-ene reaction by RFP with blue light, which triggered gelation that proceeds over about 5 min at 36 °C after an initial small change in modulus upon light exposure. Gel transparency was also evaluated, and the HA gel exhibited over 80% transmittance in the visible spectrum. The degradation and protein release kinetics of the photo-crosslinked HA hydrogel are also presented. The capacity of blue light to initiate thiol-ene reaction was equal to or more effective than UV light of the same energy. The cytocompatibility of hydrogels was evaluated using corneal fibroblasts, and the light-induced fabrication procedure and resultant gel materials did not affect cell viability. The results indicate that an RFP-based, BL-initiated photo-reaction to gelate HA may be an effective and promising modality for applications where in situ gelation is desired.

  View details for DOI 10.1016/j.reactfunctpolym.2018.06.010

  View details for PubMedID 32256185

  View details for PubMedCentralID PMC7111509

• Immobilization of growth factors to collagen surfaces using visible light. Biomacromolecules Fernandes Cunha, G. M., Lee, H. J., Kumar, A., Kreymerman, A., Heilshorn, S. C., Myung, D. 2017

  Abstract

  In the treatment of traumatic injuries, burns, and ulcers of the eye, inadequate epithelial tissue healing remains a major challenge. Wound healing is a complex process involving the temporal and spatial interplay between cells and their extracellular milieu. It can be impaired by a variety of causes including infection, poor circulation, loss of critical cells and/or proteins, and a deficiency in normal neural signaling (e.g. neurotrophic ulcers). Ocular anatomy is particularly vulnerable to lasting morbidity from delayed healing, whether it be scarring or perforation of the cornea, destruction of the conjunctival mucous membrane, or cicatricial changes to the eyelids and surrounding skin. Therefore, there is a major clinical need for new modalities for controlling and accelerating wound healing, particularly in the eye. Collagen matrices have long been explored as scaffolds to support cell growth as both two-dimensional coatings and substrates, as well as three-dimensional matrices. Meanwhile, the immobilization of growth factors to various substrates has also been extensively studied as a way to promote enhanced cellular adhesion and proliferation. Herein we present a new strategy for photochemically immobilizing growth factors to collagen using riboflavin as a photosensitizer and exposure to visible light (~458 nm). epidermal growth factor (EGF) was successfully bound to collagen-coated surfaces as well as directly to endogenous collagen from porcine corneas. The initial concentration of riboflavin and EGF, as well as the blue light exposure time, were keys to the successful binding of growth factor to these surfaces. The photocrosslinking reaction increased EGF residence time on collagen surfaces over seven days. EGF activity was maintained after the photocrosslinking reaction with a short duration of pulsed blue light exposure time. Bound EGF accelerated in vitro corneal epithelial cell proliferation and migration and maintained normal cell phenotype. Additionally, the treated surfaces were cytocompatible, and the photocrosslinking reaction was proven to be safe, preserving nearly 100% cell viability. These results suggest that this general approach is safe and versatile may be used for targeting and immobilizing bioactive factors onto collagen matrices in a variety of applications, including in the presence of live, seeded cells or in vivo onto endogenous extracellular matrix collagen.

  View details for PubMedID 28799757

• Clinical Application of a Smartphone-Based Ophthalmic Camera adapter in Under-Resourced Settings in Nepal. Journal of mobile technology in medicine Mercado, C., Welling, J., Oliva, M., Li, J., Gurung, R., Ruit, S., Tabin, G., Chang, D., Thapa, S., Myung, D. 2017; 6 (3): 34?42

  Abstract

  The ability to obtain high quality ocular images utilizing smartphone technology is of special interest in under-resourced parts of the world where traditional ocular imaging devices are cost-prohibitive, difficult to transport, and require a trained technician for operation.The purpose of this study was to explore potential anterior and posterior segment ocular imaging use cases for a smartphone-based ophthalmic camera adapter (Paxos Scope, Digisight Technologies, San Francisco, CA, USA) in under-resourced settings in Nepal.From September to November of 2015 we utilized the Paxos Scope smartphone camera adapter coupled with an iPhone 5 to explore anterior and posterior segment clinical applications for this mobile technology. We used the device at a tertiary eye care facility, a rural eye hospital and a rural cataract outreach camp. We tested the device's capability for high quality photo-documentation in clinic, in the operating room, and in the outreach camp setting. Images were automatically uploaded to a secure, cloud-based electronic medical record system that facilitated sharing of images with other providers for telemedicine purposes.Herein we present 17 ocular images documenting a wide variety of anterior and posterior segment pathology using the Paxos Scope from clinical cases seen in a variety of settings in Nepal.We found the quality of both the anterior and posterior segment images to be excellent in the clinic, the operating room, and the outreach camp settings. We found the device to be versatile and user-friendly, with a short learning curve. The Paxos Scope smartphone camera adapter may provide an affordable, high-quality, mobile ocular imaging option for under-resourced parts of the world.

  View details for DOI 10.7309/jmtm.6.3.6

  View details for PubMedID 33603897

  View details for PubMedCentralID PMC7888986

• Clinical Application of a Smartphone-Based Ophthalmic Camera Adapter in Under-Resourced Settings in Nepal Journal of Mobile Technology in Medicine Mercado, C., Welling, J., Oliva, M., Li, J., Gurung, R., Ruit, S., Tabin, G., Chang, D., Thapa, S., Myung, D. 2017; 6 (3): 34-42

  View details for DOI 10.7309/jmtm.6.3.6

• 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., 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

• Tethering Growth Factors to Collagen Surfaces Using Copper-free Click Chemistry: Surface Characterization and In Vitro Biological Response. ACS applied materials & interfaces Lee, H. J., Fernandes-Cunha, G., Putra, I., Koh, W. G., Myung, D. 2017

  Abstract

  Surface modifications with tethered growth factors have mainly been applied to synthetic polymeric biomaterials in well-controlled, acellular settings, followed by seeding with cells. The known bio-orthogonality of copper-free click chemistry provides an opportunity to not only use it in vitro to create scaffolds or pro-migratory tracks in the presence of living cells, but also potentially apply it to living tissues directly as a coupling modality in situ. In this study, we studied the chemical coupling of growth factors to collagen using biocompatible copper-free click chemistry and its effect on the enhancement of growth factor activity in vitro. We verified the characteristics of modified epidermal growth factor (EGF) using mass spectrometry and EGF/EGF receptor binding assay, and chemical immobilization of EGF on collagen was also evaluated by copper-free click chemistry using surface x-ray photoelectron spectroscopy (XPS), surface plasmon resonance (SPR) spectroscopy, and enzyme-linked immunosorbent assay (ELISA). We found that the anchoring was non-cytotoxic, biocompatible, and sufficiently rapid for clinical application. Moreover, the surface-immobilized EGF has significant effects on epithelial cell attachment and proliferation. Our results demonstrate the possibility of copper-free click chemistry as a tool for covalent bonding of growth factors to extracellular matrix collagen and the potential effectiveness of immobilized EGF in this setting. This approach is a novel and potentially clinically useful application of copper-free click chemistry as a way of directly anchoring growth factors to collagen and foster epithelial wound healing.

  View details for PubMedID 28598594

• 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

• 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 ? 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

• Comparative In vitro Cytotoxicity of Artificial Tears JSM Ophthalmology Zhen, L., Myung, D., Yu, C. Q., Ta, C. N. 2015; 3 (1): 1-6
• Grafting of Cross-Linked Hydrogel Networks to Titanium Surfaces ACS APPLIED MATERIALS & INTERFACES Muir, B. V., Myung, D., Knoll, W., Frank, C. W. 2014; 6 (2): 958-966

  Abstract

  The performance of medical implants and devices is dependent on the biocompatibility of the interfacial region between tissue and the implant material. Polymeric hydrogels are attractive materials for use as biocompatible surface coatings for metal implants. In such systems, a factor that is critically important for the longevity of an implant is the formation of a robust bond between the hydrogel layer and the implant metal surface and the ability for this assembly to withstand physiological conditions. Here, we describe the grafting of cross-linked hydrogel networks to titanium surfaces using grit-blasting and subsequent chemical functionalization using a silane-based adhesion promoter. Metal surface characterization was carried out using profilometry, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) analysis. Hydrogel layers composed of poly(ethylene glycol)-dimethacrylate (PEG-DMA), poly(2-hydroxyethylmethacrylate) (PHEMA), or poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) semi-interpenetrating polymer networks (semi-IPNs) have been prepared. The mechanical properties of these hydrogel-metal assemblies have been characterized using lap-shear measurements, and the surface morphology was studied by SEM and EDX. We have shown that both high surface roughness and chemical functionalization are critical for adhesion of the hydrogel layer to the titanium substrate.

  View details for DOI 10.1021/am404361v

  View details for Web of Science ID 000330201900031

  View details for PubMedID 24364560

• 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)
• 3D Printed Smartphone Indirect Lens Adapter for Rapid, High Quality Retinal Imaging Journal of Mobile Technology in Medicine Myung, D., Jais, A., He, L., Blumenkranz, M., Chang, R. 2014; 3 (1)
• Pupil Size and LASIK: A Review JOURNAL OF REFRACTIVE SURGERY Myung, D., Schallhorn, S., Manche, E. E. 2013; 29 (11): 734-?

  Abstract

  To provide a literature review on the evidence both for and against pupil size as an independent predictor of adverse visual outcomes after LASIK.Peer-reviewed publications on the effect of pupil size on LASIK outcomes since 2002 are reviewed. Particular attention was paid to the following attributes of each publication: type of study, number of patients or eyes, mean age, mean level of myopia, mean pupil size, testing conditions, ablation zone diameter, presence or absence of blend zones, and mean follow-up period.Among the 19 studies examined, none correlates a persistent relationship between pupil size and night vision complaints (NVCs) beyond 3 months when LASIK was performed with a 6.0-mm optical zone or larger ablation. The studies that did explicitly determine a correlation either included some or all patients with ablation zones smaller than 6.0 mm or did not specify ablation diameter at all. Among the studies that had drawn more mixed conclusions, the studies either covered short follow-up intervals (1 to 3 months) or showed a progressive improvement in NVCs over time in a relatively small patient cohort.As keratorefractive technology continues to evolve, the role of pupil size warrants further investigation; however, based on the literature reviewed herein, modern LASIK has negated the role of the low light pupil in predicting adverse visual outcomes after LASIK outside of the early postoperative period.

  View details for DOI 10.3928/1081597X-20131021-02

  View details for Web of Science ID 000329186600002

  View details for PubMedID 24203804

• In vivo biocompatibility of two PEG/PAA interpenetrating polymer networks as corneal inlays following deep stromal pocket implantation JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE Tan, X. W., Hartman, L., Tan, K. P., Poh, R., Myung, D., Zheng, L. L., Waters, D., Noolandi, J., Beuerman, R. W., Frank, C. W., Ta, C. N., Tan, D. T., Mehta, J. S. 2013; 24 (4): 967-977

  Abstract

  This study compared the effects of implanting two interpenetrating polymer networks (IPNs) into rabbit corneas. The first (Implant 1) was based on PEG-diacrylate, the second (Implant 2) was based on PEG-diacrylamide. There were inserted into deep stromal pockets created using a manual surgical technique for either 3 or 6 months. The implanted corneas were compared with normal and sham-operated corneas through slit lamp observation, anterior segment optical coherence tomography, in vivo confocal scanning and histological examination. Corneas with Implant 1 (based on PEG-diacrylate) developed diffuse haze, ulcers and opacities within 3 months, while corneas with Implant 2 (based on PEG-diacrylamide) remained clear at 6 months. They also exhibited normal numbers of epithelial cell layers, without any immune cell infiltration, inflammation, oedema or neovascularisation at post-operative 6 month. Morphological studies showed transient epithelial layer thinning over the hydrogel inserted area and elevated keratocyte activity at 3 months; however, the epithelium thickness and keratocyte morphology were improved at 6 months. Implant 2 exhibited superior in vivo biocompatibility and higher optical clarity than Implant 1. PEG-diacrylamide-based IPN hydrogel is therefore a potential candidate for corneal inlays to correct refractive error.

  View details for DOI 10.1007/s10856-012-4848-3

  View details for Web of Science ID 000318509100013

  View details for PubMedID 23354737

  View details for PubMedCentralID PMC3620449

• Biocompatibility of poly(ethylene glycol)/poly(acrylic acid) interpenetrating polymer network hydrogel particles in RAW 264.7 macrophage and MG-63 osteoblast cell lines. Journal of biomedical materials research. Part A Yim, E. S., Zhao, B., Myung, D., Kourtis, L. C., Frank, C. W., Carter, D., Smith, R. L., Goodman, S. B. 2009; 91 (3): 894-902

  Abstract

  Hydrogel polymers comprise a novel category of synthetic materials being investigated for use in cartilage replacement. One candidate compound, a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) interpenetrating polymer network (IPN), was developed for use in corneal prostheses and was recently engineered for potential orthopedic use. The current study examined the effects of particles of this compound on two cell lines (MG-63 osteoblast-like cells and RAW 264.7 macrophages) over a 48-h time course. To mimic the effects of wear debris, particles of the compound were generated and introduced to the cells. In the MG-63 cell line, the particles had no significant effect on cell viability measured by PicoGreen assay and trypan blue exclusion. In contrast, a significant decrease in cell viability was detected in the Raw 264.7 macrophage cells at the final timepoint with the highest concentration of hydrogel (3.0% v:v). A concentration- and time-dependent increase in TNF-alpha release characteristic of other known biocompatible materials was also detected in RAW 264.7 cells, but nitric oxide and interleukin (IL)-1beta showed no response. In addition, the MG-63 cell line demonstrated no IL-6 response. Particles of the PEG/PAA IPN thus seem to stimulate biological responses similar to those in other biocompatible materials.

  View details for DOI 10.1002/jbm.a.32311

  View details for PubMedID 19072924

• Bioactive interpenetrating polymer network hydrogels that support corneal epithelial wound healing. Journal of biomedical materials research. Part A Myung, D., Farooqui, N., Zheng, L. L., Koh, W., Gupta, S., Bakri, A., Noolandi, J., Cochran, J. R., Frank, C. W., Ta, C. N. 2009; 90 (1): 70-81

  Abstract

  The development and characterization of collagen-coupled poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) interpenetrating polymer network hydrogels is described. Quantitative amino acid analysis and FITC-labeling of collagen were used to determine the amount and distribution of collagen on the surface of the hydrogels. The bioactivity of the coupled collagen was detected by a conformation-specific antibody and was found to vary with the concentration of collagen reacted to the photochemically functionalized hydrogel surfaces. A wound healing assay based on an organ culture model demonstrated that this bioactive surface supports epithelial wound closure over the hydrogel but at a decreased rate relative to sham wounds. Implantation of the hydrogel into the corneas of live rabbits demonstrated that epithelial cell migration is supported by the material, although the rate of migration and morphology of the epithelium were not normal. The results from the study will be used as a guide toward the optimization of bioactive hydrogels with promise in corneal implant applications such as a corneal onlay and an artificial cornea.

  View details for DOI 10.1002/jbm.a.32056

  View details for PubMedID 18481785

• Progress in the development of interpenetrating polymer network hydrogels POLYMERS FOR ADVANCED TECHNOLOGIES Myung, D., Waters, D., Wiseman, M., Duhamel, P., Noolandi, J., Ta, C. N., Frank, C. W. 2008; 19 (6): 647-657

  Abstract

  Interpenetrating polymer networks (IPNs) have been the subject of extensive study since their advent in the 1960s. Hydrogel IPN systems have garnered significant attention in the last two decades due to their usefulness in biomedical applications. Of particular interest are the mechanical enhancements observed in "double network" IPN systems which exhibit nonlinear increases in fracture properties despite being composed of otherwise weak polymers. We have built upon pioneering work in this field as well as in responsive IPN systems to develop an IPN system based on end-linked poly-(ethylene glycol) (PEG) and loosely crosslinked poly(acrylic acid) (PAA) with hydrogen bond-reinforced strain-hardening behavior in water and high initial Young's moduli under physiologic buffer conditions through osmotically induced pre-stress. Uniaxial tensile tests and equilibrium swelling measurements were used to study PEG/PAA IPN hydrogels having second networks prepared with varying crosslinking and photoinitiator content, pH, solids content, and comonomers. Studies involving the addition of non-ionic comonomers and neutralization of the second network showed that template polymerization appears to be important in the formation of mechanically enhanced IPNs.

  View details for DOI 10.1002/pat.1134

  View details for Web of Science ID 000257014100025

  View details for PubMedCentralID PMC2745247

• Development of hydrogel-based keratoprostheses: A materials perspective 234th National Meeting of the American-Chemical-Society Myung, D., Duhamel, P., Cochran, J. R., Noolandi, J., Ta, C. N., Frank, C. W. WILEY-BLACKWELL. 2008: 735?41

  Abstract

  Research and development of artificial corneas (keratoprostheses) in recent years have evolved from the use of rigid hydrophobic materials such as plastics and rubbers to hydrophilic, water-swollen hydrogels engineered to support not only peripheral tissue integration but also glucose diffusion and surface epithelialization. The advent of the AlphaCor core-and-skirt hydrogel keratoprosthesis has paved the way for a host of new approaches based on hydrogels and other soft materials that encompass a variety of materials preparation strategies, from synthetic homopolymers and copolymers to collagen-based bio-copolymers and, finally, interpenetrating polymer networks. Each approach represents a unique strategy toward the same goal: to develop a new hydrogel that mimics the important properties of natural donor corneas. We provide a critical review of these approaches from a materials perspective and discuss recent experimental results. While formidable technical hurdles still need to be overcome, the rapid progress that has been made by investigators with these approaches is indicative that a synthetic donor cornea capable of surface epithelialization is now closer to becoming a clinical reality.

  View details for DOI 10.1021/bp070476n

  View details for PubMedID 18422366

• Glucose-permeable interpenetrating polymer network hydrogels for corneal implant applications: A pilot study CURRENT EYE RESEARCH Myung, D., Farooqui, N., Waters, D., Schaber, S., Koh, W., Carrasco, M., Noolandi, J., Frank, C. W., Ta, C. N. 2008; 33 (1): 29-43

  Abstract

  Epithelialization of a keratoprosthesis requires that the implant material be sufficiently permeable to glucose. We have developed a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) interpenetrating polymer network (IPN) hydrogel that can provide adequate passage of glucose from the aqueous humor to the epithelium in vivo. A series of PEG/PAA IPNs with varying PEG macromonomer molecular weights were synthesized and evaluated through swelling studies to determine their water content and diffusion experiments to assess their permeability to glucose. One of the PEG/PAA hydrogels prepared in this study had a glucose diffusion coefficient nearly identical to that of the human cornea (approximately 2.5 x 10(-6) cm(2)/sec). When implanted intrastromally in rabbit corneas, this hydrogel was retained and well-tolerated in 9 out of 10 cases for a period of 14 days. The retained hydrogels stayed optically clear and the epithelium remained intact and multilayered, indicating that the material facilitated glucose transport from the aqueous humor to the anterior part of the eye. The results from these experiments indicate that PEG/PAA hydrogels are promising candidates for corneal implant applications such as keratoprostheses and intracorneal lenses, and that the PEG/PAA IPN system in general is useful for creating permeable substrates for ophthalmic and other biomedical applications.

  View details for DOI 10.1080/02713680701793930

  View details for PubMedID 18214741

• Progress in the development of interpenetrating polymer network hydrogels. Polymers for advanced technologies Myung, D., Waters, D., Wiseman, M., Duhamel, P. E., Noolandi, J., Ta, C. N., Frank, C. W. 2008; 19 (6): 647?57

  Abstract

  Interpenetrating polymer networks (IPNs) have been the subject of extensive study since their advent in the 1960s. Hydrogel IPN systems have garnered significant attention in the last two decades due to their usefulness in biomedical applications. Of particular interest are the mechanical enhancements observed in "double network" IPN systems which exhibit nonlinear increases in fracture properties despite being composed of otherwise weak polymers. We have built upon pioneering work in this field as well as in responsive IPN systems to develop an IPN system based on end-linked poly-(ethylene glycol) (PEG) and loosely crosslinked poly(acrylic acid) (PAA) with hydrogen bond-reinforced strain-hardening behavior in water and high initial Young's moduli under physiologic buffer conditions through osmotically induced pre-stress. Uniaxial tensile tests and equilibrium swelling measurements were used to study PEG/PAA IPN hydrogels having second networks prepared with varying crosslinking and photoinitiator content, pH, solids content, and comonomers. Studies involving the addition of non-ionic comonomers and neutralization of the second network showed that template polymerization appears to be important in the formation of mechanically enhanced IPNs.

  View details for PubMedID 19763189

• Design and fabrication of an artificial cornea based on a photolithographically patterned hydrogel construct BIOMEDICAL MICRODEVICES Myung, D., Koh, W., Bakri, A., Zhang, F., Marshall, A., Ko, J., Noolandi, J., Carrasco, M., Cochran, J. R., Frank, C. W., Ta, C. N. 2007; 9 (6): 911-922

  Abstract

  We describe the design and fabrication of an artificial cornea based on a photolithographically patterned hydrogel construct, and demonstrate the adhesion of corneal epithelial and fibroblast cells to its central and peripheral components, respectively. The design consists of a central "core" optical component and a peripheral tissue-integrable "skirt." The core is composed of a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) double-network with high strength, high water content, and collagen type I tethered to its surface. Interpenetrating the periphery of the core is a microperforated, but resilient poly(hydroxyethyl acrylate) (PHEA) hydrogel skirt that is also surface-modified with collagen type I. The well-defined microperforations in the peripheral component were created by photolithography using a mask with radially arranged chrome discs. Surface modification of both the core and skirt elements was accomplished through the use of a photoreactive, heterobifunctional crosslinker. Primary corneal epithelial cells were cultured onto modified and unmodified PEG/PAA hydrogels to evaluate whether the central optic material could support epithelialization. Primary corneal fibroblasts were seeded onto the PHEA hydrogels to evaluate whether the peripheral skirt material could support the adhesion of corneal stromal cells. Cell growth in both cases was shown to be contingent on the covalent tethering of collagen. Successful demonstration of cell growth on the two engineered components was followed by fabrication of core-skirt constructs in which the central optic and peripheral skirt were synthesized in sequence and joined by an interpenetrating diffusion zone.

  View details for DOI 10.1007/s10544-006-9040-4

  View details for PubMedID 17237989

• Histological processing of pH-sensitive hydrogels used in corneal implant applications JOURNAL OF HISTOTECHNOLOGY Farooqui, N., Myung, D., Koh, W., Masek, M., Dalal, R., Carrasco, M. R., Noolandi, J., Frank, C. W., Ta, C. N. 2007; 30 (3): 157-163

  View details for Web of Science ID 000258533600003

• Prospective randomized comparison of 1-day versus 3-day application of topical levofloxacin in eliminating conjunctival flora. European journal of ophthalmology Ta, C. N., Sinnar, S., He, L., Myung, D., Mino De Kaspar, H. 2007; 17 (1): 689-695

  Abstract

  To compare efficacy of a 1-day versus 3-ayapplication of topical levofloxacin in reducing ocular surface bacteria.In this prospective randomized controlled trial, 100 volunteer patients (50 per group) were assigned to receive topical 0.5% levofloxacin four times daily for 1 day or 3 days. Conjunctival cultures were obtained prior to (T0) and after the application of antibiotics (T1). Additionally, all patients received topical levofloxacin at 5-minute intervals for three applications (T2), followed by two drops of topical 5% povidone-iodine (T3). Conjunctival cultures were obtained at timepoints T2 and T3.A 1-day application of topical levofloxacin significantly reduced (p = 0.0004) the number of eyes with positive conjunctival cultures from 41 eyes (82%) to 23 eyes (46%). Similarly, a 3-day application significantly reduced (p = 0.0001) the positive culture rate from 37 eyes (74%) to 17 eyes (34%). Two drops of povidone-iodine further reduced the positive culture rate for both groups to 20% (10 eyes for each group). There was no significant difference in positive culture rate between the 1-day and 3-day groups at T0 (p = 0.4689), T1 (p = 0.3074), T2 (p = 0.6706), or T3 (p = 1.000).The application of topical 0.5% levofloxacin for 1 or 3 days significantly reduced the number of eyes with positive conjunctival cultures. The addition of 5% povidone-iodine further eliminated bacteria from the conjunctiva. The application of levofloxacin for 1 day appears to be as effective as a 3-day application.

  View details for DOI 10.5301/EJO.2008.3555

  View details for PubMedID 28221506

• Biomimetic strain hardening in interpenetrating polymer network hydrogels POLYMER Myung, D., Koh, W., Ko, J., Hu, Y., Carrasco, M., Noolandi, J., Ta, C. N., Frank, C. W. 2007; 48 (18): 5376-5387

  View details for DOI 10.1016/j.polymer.2007.06.070

  View details for Web of Science ID 000249712800021

• Glucose permeability of human, bovine, and porcine corneas in vitro OPHTHALMIC RESEARCH Myung, D., Derr, K., Huie, P., Noolandi, J., Ta, K. P., Ta, C. N. 2006; 38 (3): 158-163

  Abstract

  To measure glucose flux across human, bovine, and porcine corneas and to determine the diffusion coefficient of each type of cornea.Diffusion of glucose across human (n = 8), bovine (n = 7), and pig corneas (n = 8) was measured using a modified blind well chamber apparatus (Boyden chamber). Dialysis membranes (n = 7) and nonporous Mylar membranes (n = 7) were used as positive and negative controls, respectively. Glucose concentrations were measured at 30-min intervals with a commercially available glucose meter.The diffusion of glucose through corneas in vitro was calculated by a simple Fickian diffusion model. The diffusion coefficient of glucose is highest for the human cornea (D(HC) = 3.0 +/- 0.2 x 10(-6) cm(2)/s) followed by porcine corneas (D(PC) = 1.8 +/- 0.6 x 10(-6) cm(2)/s) and bovine corneas (D(BC) = 1.6 +/- 0.1 x 10(-6) cm(2)/s) (p < 0.05). The diffusion coefficients of all tested corneas were significantly higher (p < 0.05) than that of dialysis membrane (D(DM) = 3.4 +/- 0.2 x 10(-7) cm(2)/s).The glucose diffusion coefficients of human, bovine, and porcine corneas are on the order of 10(-6). Human corneas have higher permeability to glucose than either porcine or bovine corneas.

  View details for DOI 10.1159/000090726

  View details for PubMedID 16401912