Using a Macro Lens for Anterior Segment Imaging in Rural Panama.

Background: Visual impairment, specifically anterior segment pathology, presents a significant burden of disease in the world. Introduction: Inexpensive tools are necessary to improve eye health of residents in developing countries where care is difficult to access. Our study aimed at determining whether a $5 macro lens attached to a smartphone camera is an effective anterior segment imaging method for screening diseases. Materials and Methods: Fifty four (n = 54) patients had anterior segment imaging performed by using an Easy Macro lens and an iPhone. Imaging was performed at the Floating Doctors' mobile clinic sites in Panama. Images were sent back and graded by two board-certified ophthalmologists using a modified version of the FOTO-ED scale. Statistical analysis was performed by using a Wilcoxon signed-rank test to compare grades between the two imaging modalities. Results: There was no significant difference in overall clinical utility of images obtained by the iPhone versus Easy Macro lens. The iPhone was significantly superior in imaging of the lens and conjunctiva, whereas the Easy Macro lens was superior in regards to the anterior chamber, iris, and lens. Discussion: The imaging modality that best captures pathology is dependent on what part of the anterior segment is being examined. An imaging protocol with a pair of images, one from a smartphone and one from a macro lens, would have significant clinical utility. Conclusion: Our study demonstrates how minimally trained users can deliver effective eye screening via a telemedicine-based approach in a resource-deprived setting. Future directions would be to develop a telemedicine protocol and determine whether it improves clinically measurable outcomes in patients.

Animal models of radiation retinopathy - From teletherapy to brachytherapy.

Radiation retinopathy is a serious vision-impairing complication of radiation therapy used to treat ocular tumors. Characterized by retinal vasculopathy and subsequent retinal damage, the first sign of radiation retinopathy is the preferential loss of vascular endothelial cells. Ensuing ischemia leads to retinal degradation and late stage neovascularization. Despite the established disease progression, the pathophysiology and cellular mechanisms contributing to radiation retinopathy remain unclear. Clinical experience and basic research for other retinal vasculopathies, such as diabetic retinopathy and retinopathy of prematurity, can inform our understanding of radiation retinopathy; however, the literature investigating the fundamental mechanisms in radiation retinopathy is limited. Treatment trials have shown modest success but, ultimately, fail to address the cellular events that initiate radiation retinopathy. Animal models of radiation retinopathy could provide means to identify effective therapies. Here, we review the literature for all animal models of radiation retinopathy, summarize anatomical highlights pertaining to animal models, identify additional physiological factors to consider when investigating radiation retinopathy, and explore the use of clinically relevant tests for studying in vivo models of radiation retinopathy. We encourage further investigation into the mechanistic characterization of radiation retinopathy in the hope of discovering novel treatments.

Optimizing precision in toric lens selection by combining keratometry techniques.

PURPOSE: To increase precision in toric intraocular lens selection by reducing the frequency of outliers that arise from technology-dependent variability during the preoperative assessment for routine cataract surgery. METHODS: Mean preoperative values for absolute sphere, amount of astigmatism, and steepest cylindrical axis were obtained for 87 eyes (54 patients) each with a manual keratometer and four automated keratometers. The mean sphere, amount of astigmatism, and steepest cylindrical axis across five technologies for each eye were defined as the meld sphere, meld astigmatism, and meld axis, respectively. Each technology was evaluated against the meld by Bland­Altman analysis, Student's paired t test, and correlation coefficients. Further comparison between individual technologies and the meld quantified the number of outlier measurements each technology produced. RESULTS: The number of outliers between individual keratometers and the meld differed with specific measurement of sphere, axis, or amount of astigmatism. Although statistical analysis using Bland­Altman plots, correlation coefficients, and paired t tests suggested insignificant difference from meld measurements for each parameter, precision-guided analysis presented more clinically significant outliers. The number of outliers can be reduced for sphere (range: 2%-46% to 1%-6%), astigmatism (range: 6%-23% to 0%-2%), and axis outliers (range: 15%-27% to 3%-6%) by averaging measurements from automated and manual keratometers. CONCLUSIONS: Although multiple keratometry technologies produced similar, average measurements, the authors found a disturbing number of outliers that may be overlooked when employing a single technology. Measurement errors can be dramatically reduced by averaging measurements from manual keratometry with any automated technology to make toric lens selection more precise.

Imaging performance of portable and conventional ultrasound imaging technologies for ophthalmic applications.

PURPOSE: The aim of this study was to evaluate the imaging capabilities of Butterfly iQ with conventional ophthalmic (piezoelectric) ultrasound (COU) for ophthalmic imaging. METHODS: Custom phantom molds were designed and imaged with Butterfly iQ and COU to compare spatial resolution capabilities. To evaluate the clinical imaging performance of Butterfly iQ and COU, a survey containing pathological conditions from human subjects, imaged with both Butterfly iQ and COU probes, was given to three retina specialists and graded on image detail, resolution, quality, and diagnostic confidence on a ten-point Likert scale. Kruskal-Wallis analysis was performed for survey responses. RESULTS: Butterfly iQ and COU had comparable capabilities for imaging small axial and lateral phantom features (down to 0.1 mm) of high and low acoustic reflectivity. One of three retina specialists demonstrated a statistically significant preference for COU related to resolution, detail, and diagnostic confidence, but the remaining graders showed no significant preference for Butterfly iQ or COU across all sample images presented. CONCLUSION: The emergence of portable ultrasound probes offers an affordable alternative to COU technologies with comparable qualitative imaging resolution down to 0.1 mm. These findings suggest the value to further study the use of portable ultrasound systems and their utility in routine eye care.

Deep Learning Assisted Imaging Methods to Facilitate Access to Ophthalmic Telepathology.

Purpose: To investigate the use of super-resolution imaging techniques to enable telepathology using low-cost commercial cameras. Design: Experimental study. Participants: A total of 139 ophthalmic pathology slides obtained from the Ophthalmic Pathology service at the University of California, Irvine. Methods: Denoising Diffusion Probabilistic Model (DDPM) was developed to predict super-resolution pathology slide images from low-resolution inputs. The model was pretrained using 150 000 images randomly sampled from the ImageNet dataset. Patch aggregation was used to generate large images with DDPM. The performance of DDPM was evaluated against that of generative adversarial networks (GANs) and Robust UNet, which were also trained on the same dataset. Main Outcome Measures: The performance of models trained to generate super-resolution output images from low-resolution input images can be evaluated by using the mean squared error (MSE) and Structural Similarity Index Measure (SSIM), as well as subjective grades provided by expert pathologist graders. Results: In total, our study included 110 training images, 9 validation images, and 20 testing images. The objective performance scores were averaged over patches generated from 20 test images. The DDPM-based approach with pretraining produced the best results, with an MSE score of 1.35e-5 and an SSIM score of 0.8987. A qualitative analysis of super-resolution images was conducted by expert 3 pathologists and 1 expert ophthalmic microscopist, and the average accuracy of identifying the correct ground truth images ranged from 25% to 70% (with an average accuracy of 46.5%) for widefield images and 25% to 60% (with an average accuracy of 38.25%) for individual patches. Conclusions: The DDPM-based approach with pretraining is assessed to be effective at super-resolution prediction for ophthalmic pathology slides both in terms of objective and subjective measures. The proposed methodology is expected to decrease the reliance on costly slide scanners for acquiring high-quality pathology slide images, while also streamlining clinical workflow and expanding the scope of ophthalmic telepathology. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparison of a custom Photogrammetry for Anatomical CarE (PHACE) system with other Low- Cost Facial Scanning Devices.

Purpose: To compare a custom Photogrammetry for Anatomical CarE (PHACE) system with other cost-effective 3-dimensional (3D) facial scanning systems to objectively characterize morphology and volume of periorbital and adnexal anatomy. Methods: The imaging systems evaluated include the low-cost custom PHACE system and commercial software product for the iPhone called Scandy Pro (iScandy) application (Scandy, USA), and the mid-priced Einscan Pro 2X (Shining3D Technologies, China) device and Array of Reconstructed Cameras 7 (ARC7) facial scanner (Bellus3D, USA). Imaging was performed on a manikin facemask and humans with various Fitzpatrick scores. Scanner attributes were assessed using mesh density, reproducibility, surface deviation, and emulation of 3D printed phantom lesions affixed above the superciliary arch (brow line). Results: The Einscan served as a reference for lower cost imaging systems because it qualitatively and quantitatively renders facial morphology with the highest mesh density, reproducibility (0.13 ± 0.10 mm), and volume recapitulation (approximately 2% of 33.5 µL). Compared to the Einscan, the PHACE system (0.35 ± 0.03 mm, 0.33 ± 0.16 mm) demonstrated non-inferior mean accuracy and reproducibility root mean square (RMS) compared to the iScandy (0.42 ± 0.13 mm, 0.58 ± 0.09 mm), and significantly more expensive ARC7 (0.42 ± 0.03 mm, 0.26 ± 0.09 mm). Similarly, the PHACE system showed non-inferior volumetric modeling when rendering a 124 µL phantom lesion compared to the iScandy and more costly ARC7 (mean percent difference from the Einscan: 4.68 ± 3.73%, 9.09 ± 0.94%, and 21.99 ± 17.91% respectively). Conclusions: The affordable PHACE system accurately measures periorbital soft tissue as well as other established mid-cost facial scanning systems. Additionally, the portability, affordability, and adaptability of PHACE can facilitate widespread adoption of 3D facial anthropometric technology as an objective measurement tool in ophthalmology.

Vitreoretinal Surgical Instrument Tracking in Three Dimensions Using Deep Learning.

Purpose: To evaluate the potential for artificial intelligence-based video analysis to determine surgical instrument characteristics when moving in the three-dimensional vitreous space. Methods: We designed and manufactured a model eye in which we recorded choreographed videos of many surgical instruments moving throughout the eye. We labeled each frame of the videos to describe the surgical tool characteristics: tool type, location, depth, and insertional laterality. We trained two different deep learning models to predict each of the tool characteristics and evaluated model performances on a subset of images. Results: The accuracy of the classification model on the training set is 84% for the x-y region, 97% for depth, 100% for instrument type, and 100% for laterality of insertion. The accuracy of the classification model on the validation dataset is 83% for the x-y region, 96% for depth, 100% for instrument type, and 100% for laterality of insertion. The close-up detection model performs at 67 frames per second, with precision for most instruments higher than 75%, achieving a mean average precision of 79.3%. Conclusions: We demonstrated that trained models can track surgical instrument movement in three-dimensional space and determine instrument depth, tip location, instrument insertional laterality, and instrument type. Model performance is nearly instantaneous and justifies further investigation into application to real-world surgical videos. Translational Relevance: Deep learning offers the potential for software-based safety feedback mechanisms during surgery or the ability to extract metrics of surgical technique that can direct research to optimize surgical outcomes.

Optimization of a Novel Automated, Low Cost, Three-Dimensional Photogrammetry System (PHACE).

Introduction: Clinical tools are neither standardized nor ubiquitous to monitor volumetric or morphological changes in the periorbital region and ocular adnexa due to pathology such as oculofacial trauma, thyroid eye disease, and the natural aging process. We have developed a low-cost, three dimensionally printed PHotogrammetry for Automated CarE (PHACE) system to evaluate three-dimensional (3D) measurements of periocular and adnexal tissue. Methods: The PHACE system uses two Google Pixel 3 smartphones attached to automatic rotating platforms to image a subject's face through a cutout board patterned with registration marks. Photographs of faces were taken from many perspectives by the cameras placed on the rotating platform. Faces were imaged with and without 3D printed hemispheric phantom lesions (black domes) affixed on the forehead above the brow. Images were rendered into 3D models in Metashape (Agisoft, St. Petersburg, Russia) and then processed and analyzed in CloudCompare (CC) and Autodesk's Meshmixer. The 3D printed hemispheres affixed to the face were then quantified within Meshmixer and compared to their known volumes. Finally, we compared digital exophthalmometry measurements with results from a standard Hertel exophthalmometer in a subject with and without an orbital prosthesis. Results: Quantification of 3D printed phantom volumes using optimized stereophotogrammetry demonstrated a 2.5% error for a 244µL phantom, and 7.6% error for a 27.5µL phantom. Digital exophthalmometry measurements differed by 0.72mm from a standard exophthalmometer. Conclusion: We demonstrated an optimized workflow using our custom apparatus to analyze and quantify oculofacial volumetric and dimensions changes with a resolution of 244µL. This apparatus is a low-cost tool that can be used in clinical settings to objectively monitor volumetric and morphological changes in periorbital anatomy.

Genome editing in the treatment of ocular diseases.

Genome-editing technologies have ushered in a new era in gene therapy, providing novel therapeutic strategies for a wide range of diseases, including both genetic and nongenetic ocular diseases. These technologies offer new hope for patients suffering from previously untreatable conditions. The unique anatomical and physiological features of the eye, including its immune-privileged status, size, and compartmentalized structure, provide an optimal environment for the application of these cutting-edge technologies. Moreover, the development of various delivery methods has facilitated the efficient and targeted administration of genome engineering tools designed to correct specific ocular tissues. Additionally, advancements in noninvasive ocular imaging techniques and electroretinography have enabled real-time monitoring of therapeutic efficacy and safety. Herein, we discuss the discovery and development of genome-editing technologies, their application to ocular diseases from the anterior segment to the posterior segment, current limitations encountered in translating these technologies into clinical practice, and ongoing research endeavors aimed at overcoming these challenges.

Quantitative cone contrast threshold testing in patients with differing pathophysiological mechanisms causing retinal diseases.

BACKGROUND: Cone contrast threshold testing (CCT) provides quantitative measurements of color and contrast function to reveal changes in vision quality that are not standard endpoints in clinical trials. We utilize CCT to measure visual function in patients with multiple sclerosis (MS), age-related macular degeneration (AMD), epiretinal membrane (ERM), and retinal vein occlusion (RVO). METHODS: Retrospective data was gathered from 237 patients of the Gavin Herbert Eye Institute. Subjects included 17 patients with MS, 45 patients with AMD, 41 patients with ERM, 11 patients with RVO, and 123 healthy controls. Patients underwent the primary measurement outcome, CCT testing, as well as Sloan visual acuity test and spectral domain optical coherence tomography during normal care. RESULTS: Color and contrast deficits were present in MS patients regardless of history of optic neuritis. AMD with intermediate or worse disease demonstrated reduced CCT scores. All 3 stages of ERM demonstrated cone contrast deficits. Despite restoration of visual acuity, RVO-affected eyes demonstrated poorer CCT performance than unaffected fellow eyes. CONCLUSIONS: CCT demonstrates color and contrast deficits for multiple retinal diseases with differing pathophysiology. Further prospective studies of CCT in other disease states and with larger samples sizes is warranted.

Seeing invisible light: 2-photon microperimetry to measure visual function.

Purpose: The accuracy of conventional visual function tests, which emit visible light, decreases in patients with corneal scars, cataracts, and vitreous hemorrhages. In contrast, infrared (IR) light exhibits greater tissue penetrance than visible light and is less susceptible to optical opacities. We therefore compared conventional visual function tests against infrared 2-phton microperimetry (2PM-IR) in a subject with a brunescent nuclear sclerotic and posterior subcapsular cataract before and after cataract surgery. Methods: Testing using infrared light microperimetry from a novel device (2PM-IR), visible light microperimetry from a novel device (2PM-Vis), conventional microperimetry, and the cone contrast threshold (CCT) test were performed before and after cataract surgery. Results: Retinal sensitivity assessed using 2PM-IR, 2PM-Vis, and cMP improved by 3.4 dB, 17.4 dB, and 18 dB, respectively. Cone contrast threshold testing improved for the S-cone, M-cone, and l-cone by 111, 14, and 30. Conclusions and Importance: 2PM-IR, unlike conventional visual function tests, showed minimal variability in retinal sensitivity before and after surgery. Thus, IR visual stimulation may provide a more accurate means of measuring neurosensory retinal function by circumventing optical media opacities, aiding in the diagnosis of early macular disease.

A case report of cystoid macular edema, uveitis and vitreomacular traction in a patient taking Anastrozole.

PURPOSE: To report a case of cystoid macular edema, uveitis, and vitreomacular traction in a patient with a history of breast cancer and taking anastrozole. OBSERVATIONS: A 73-year-old female with a history of estrogen receptor-positive breast cancer and treatment with anastrozole presented with bilateral blurry vision, photophobia, and eye soreness. Optical coherence tomography (OCT) of both maculae revealed vitreomacular traction (VMT), an epiretinal membrane, cystoid macular edema (CME) in the right eye, and drusen without subretinal fluid bilaterally. Although later, macular OCT did show evidence of cystoid intraretinal spaces in the left eye as well. Fluorescein angiography showed bilateral petaloid leakage, bilateral slow disc leaking, as well as peripheral leakage in the right eye. Anastrozole was discontinued and, subsequent macular OCT showed release of VMT in the right eye, and eventual resolution of intraretinal cystoid spaces bilaterally. CONCLUSIONS AND IMPORTANCE: Stopping of anastrozole was associated in resolution of refractory CME in a patient on aromatase inhibitor therapy for breast cancer. It is therefore important to consider anastrozole and other aromatase inhibitor drugs as possible factors predisposing patients to the development of CME.

Treatment of Choroidal Metastasis from Epidermal Growth Factor Mutant Non-Small Cell Lung Cancer with First-line Osimertinib Therapy.

PURPOSE: To illustrate the regression of a metastatic lesion through ophthalmic imaging and correlating findings with standard chest imaging and treatment with osimertinib, an oral chemotherapy agent specific to Epidermal Growth Factor Receptor + Non-small Cell Lung Cancer (EGFR+ NSCLC). CASE REPORT: A 63-year-old Asian male presented to ophthalmology with a complaint of left blurry vision. Initial ophthalmic exam revealed a choroidal lesion and imaging results highlighted a spiculated lung mass with brain and bony metastases. Osimertinib was chosen for its specificity and ability to cross the blood-brain barrier. Follow-up ophthalmic and radiographic imaging were repeated over the course of treatment. CONCLUSION: After the initiation of osimertinib, ophthalmic and computed tomography imaging highlighted the regression of the ocular metastatic disease and primary malignancy, respectively.Osimertinib is an effective first-line treatment of EGFR+ NSCLC and corresponding metastatic sites. Additionally, ophthalmic imaging can be used to monitor general response to chemotherapy agents when ocular metastasis is identified.

The Prospects for Retinal Organoids in Treatment of Retinal Diseases.

Retinal degeneration (RD) is a significant cause of incurable blindness worldwide. Photoreceptors and retinal pigmented epithelium are irreversibly damaged in advanced RD. Functional replacement of photoreceptors and/or retinal pigmented epithelium cells is a promising approach to restoring vision. This paper reviews the current status and explores future prospects of the transplantation therapy provided by pluripotent stem cell-derived retinal organoids (ROs). This review summarizes the status of rodent RD disease models and discusses RO culture and analytical tools to evaluate RO quality and function. Finally, we review and discuss the studies in which RO-derived cells or sheets were transplanted. In conclusion, methods to derive ROs from pluripotent stem cells have significantly improved and become more efficient in recent years. Meanwhile, more novel technologies are applied to characterize and validate RO quality. However, opportunity remains to optimize tissue differentiation protocols and achieve better RO reproducibility. In order to screen high-quality ROs for downstream applications, approaches such as noninvasive and label-free imaging and electrophysiological functional testing are promising and worth further investigation. Lastly, transplanted RO-derived tissues have allowed improvements in visual function in several RD models, showing promises for clinical applications in the future.

Deep learning to enable color vision in the dark.

Humans perceive light in the visible spectrum (400-700 nm). Some night vision systems use infrared light that is not perceptible to humans and the images rendered are transposed to a digital display presenting a monochromatic image in the visible spectrum. We sought to develop an imaging algorithm powered by optimized deep learning architectures whereby infrared spectral illumination of a scene could be used to predict a visible spectrum rendering of the scene as if it were perceived by a human with visible spectrum light. This would make it possible to digitally render a visible spectrum scene to humans when they are otherwise in complete "darkness" and only illuminated with infrared light. To achieve this goal, we used a monochromatic camera sensitive to visible and near infrared light to acquire an image dataset of printed images of faces under multispectral illumination spanning standard visible red (604 nm), green (529 nm) and blue (447 nm) as well as infrared wavelengths (718, 777, and 807 nm). We then optimized a convolutional neural network with a U-Net-like architecture to predict visible spectrum images from only near-infrared images. This study serves as a first step towards predicting human visible spectrum scenes from imperceptible near-infrared illumination. Further work can profoundly contribute to a variety of applications including night vision and studies of biological samples sensitive to visible light.

An in-line microfluidic blood sampling interface between patients and saline infusion systems.

This work seeks to extend the utility of microfluidics to conventional blood sampling aperati. Daily medical care of hospitalized patients demands repeated needle punctures or interfacing with a catheter to collect blood samples. Large, research grade systems can autonomously sample blood from laboratory animals; however, a disposable aperatus that can be used to repeatedly sample blood from hospitalized patients does not exist. We have designed, fabricated and demonstrated a 3-layered rigid polymer microfluidic blood sampling device with integrated polymer pinch valves for placement in-line between a patient and a saline infusion system. The blood sampler we designed seeks to mitigate sample cross contamination, reduce risks of microbial contamination associated with invasive blood sampling and improve technical ease of blood sampling. Clinical laboratory tests and microfluidic devices for rapid point-of-care-testing (POCT) of patient samples require human sampling procedures for collection of a patient sample at defined time points. The microfluidic sampling device is designed ultimately to be backwards compatible with existing clinical saline infusion protocols and function as a universal front-end blood sampling unit for the variety of microfluidic lab chips and POCT devices.

BEARING DOWN ON TREPONEMES: AN ATYPICAL PRESENTATION OF SYPHILITIC UVEITIS.

PURPOSE: To present an atypical case of syphilis that presented with findings concerning for endocarditis and valsalva retinopathy. METHODS: History and clinical examination of 42-year-old white man who presented to the emergency department with acute onset vision changes associated with gastrointestinal symptoms, otalgia, and constitutional symptoms. RESULTS: The review of this case highlights the atypical nature in which syphilis can present and can remain undiagnosed even in the face of extensive workups for other systemic conditions. CONCLUSION: We present a case of syphilis in a patient with multiorgan involvement in whom the diagnosis was made based on atypical ocular examination findings.

Multimodal Imaging in Ocular Siderosis.

Purpose: This report aims to characterize ocular changes in a case of ocular siderosis with iron toxicity using multimodal imaging and electroretinography. Methods: A 34-year-old woman presented with ocular siderosis of the left eye following penetrating injury with an iron-containing foreign body. The patient's uncorrected visual acuities were 20/60 and 20/150 in the right and left eye, respectively, with abnormal pupillary function and presence of a cataract in the left eye. She underwent successful intraocular foreign body removal and cataract surgery with no postoperative complications. Cone contrast threshold (CCT), full-field electroretinogram, spectral-domain optical coherence tomography (OCT), and OCT angiography (OCTA) were used to characterize ocular alterations preoperatively and postoperatively. Results: CCT color vision testing showed abnormal color vision, and OCTA revealed increased vascular flow density associated with the foreign body. Conclusions: CCT color vision testing, OCTA, OCT, and full-field electroretinogram can characterize retinal changes in cases of ocular siderosis.