Imaging and Diagnostics

Imaging and Diagnostics Publications

Cui Y, Zhu Y, Wang JC, Lu Y, Zeng R, Katz R, Wu DM, Vavvas DG, Husain D, Miller JW, Kim LA, Miller JB. Imaging Artifacts and Segmentation Errors With Wide-Field Swept-Source Optical Coherence Tomography Angiography in Diabetic Retinopathy. Transl Vis Sci Technol 2019;8(6):18.Abstract
Purpose: To analyze imaging artifacts and segmentation errors with wide-field swept-source optical coherence tomography angiography (SS-OCTA) in diabetic retinopathy (DR). Methods: We conducted a prospective, observational study at Massachusetts Eye and Ear from December 2018 to March 2019. Proliferative diabetic retinopathy (PDR), nonproliferative diabetic retinopathy (NPDR), diabetic patients with no diabetic retinopathy (DR), and healthy control eyes were included. All patients were imaged with a SS-OCTA and the Montage Angio (15 × 9 mm) was used for analysis. Images were independently evaluated by two graders using the motion artifact score (MAS). All statistical analyses were performed using SPSS 25.0 and R software. Results: One hundred thirty-six eyes in 98 participants with the montage image were included in the study. Patients with more severe stages of DR had higher MAS by trend test analysis ( < 0.05). The occurrence of segmentation error was 0% in the healthy group, 10.53% in the no DR group, 10.00% in the NPDR group, and 50% in the PDR group. Multivariate regression analysis showed that the severity of DR and dry eye were the major factors affecting MAS ( < 0.05). There were some modifiable artifacts that could be corrected to improve image quality. Conclusions: Wide field SS-OCTA assesses retinal microvascular changes by noninvasive techniques, yet distinguishing real alterations from artifacts is paramount to accurate interpretations. DR severity and dry eye correlated with MAS. Translational Relevance: Understanding contributing factors and methods to reduce artifacts is critical to routine use and clinical trial with wide-field SS-OCTA.
Rong AJ, Fan KC, Golshani B, Bobinski M, McGahan JP, Eliott D, Morse LS, Modjtahedi BS. Multimodal imaging features of intraocular foreign bodies. Semin Ophthalmol 2019;:1-15.Abstract
: To determine the imaging approach for evaluating intraocular foreign bodies (IOFBs) by comparing the ability of different modalities [plain film x-ray, computed tomography (CT), magnetic resonsance imaging (MRI), convetional ultrasound, and ultrasound biomicroscopy] to detect and characterize IOFBs. : Systematic review of the literature. : CT is the most practical first step for evaluating patients with suspected IOFBs because it can detect a wide range of IOFB types at small limitis of detection. MRI and ultrasound are best reserved as adjunctive tests in most cases although these tests may provide important insights especially with wood, plastic, and glass IOFBs. Imaging characteristics of metal, wood, glass, plastic, stone, concrete, and graphite IOFBs are reviewed. : Understanding the limits of detection for each IOFB type and imaging modality as well as the characteristic features of different IOFBs is of paramount importance to optimizing the management of ocular trauma patients.
Porporato N, Baskaran M, Tun TA, Sultana R, Tan M, Quah JHM, Allen JC, Perera S, Friedman DS, Cheng CY, Aung T. Understanding diagnostic disagreement in angle closure assessment between anterior segment optical coherence tomography and gonioscopy. Br J Ophthalmol 2019;Abstract
BACKGROUND/AIMS: Although being a more objective tool for assessment and follow-up of angle closure, reliability studies have reported a moderate diagnostic performance for anterior segment optical coherence tomography (OCT) technologies when comparing with gonioscopy as the reference standard. We aim to determine factors associated with diagnostic disagreement in angle closure when assessed by anterior segment swept source OCT (SS-OCT, CASIA SS-1000; Tomey, Nagoya, Japan) and gonioscopy. METHODS: Cross-sectional study. A total of 2027 phakic subjects aged ≥50 years, with no relevant previous ophthalmic history, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy and SS-OCT (128 radial scans) for the entire circumference of the angle were performed for each subject. A two-quadrant closed gonioscopic definition was used. On SS-OCT images, angle closure was defined as iridotrabecular contact (ITC) to the extent of ≥35%, ≥50% and ≥75% of the circumferential angle. Diagnostic disagreements between both methods, that is, false positives or overcalls and false negatives or undercalls were defined, respectively, as gonioscopic open/closed angles inversely assessed as closed/open by SS-OCT. RESULTS: Two hundred and seventy-two (14.7%) resulted in overcall results (false positives) when ≥50% of the angle circumference was closed using SS-OCT. These eyes had significantly wider (anterior chamber width, 11.7 vs 11.6 mm, p<0.001) and deeper (anterior chamber depth (ACD), 2.4 vs 2.2 mm, p<0.001) anterior chambers than eyes assessed by both methods as closed (true positives). Deeper ACD (OR 9.31) and lower lens vault (LV) (OR 0.04) were significantly associated with a false positive diagnosis in the multivariate analysis. Most of these cases had short (52.6%) or irregular (39%) ITC in SS-OCT images. CONCLUSIONS: We found that anterior chamber dimensions, determined by ACD and LV, were factors significantly associated with diagnostic disagreement between anterior segment SS-OCT and gonioscopy in angle closure assessment.
Sajdak BS, Salmon AE, Cava JA, Allen KP, Freling S, Ramamirtham R, Norton TT, Roorda A, Carroll J. Noninvasive imaging of the tree shrew eye: Wavefront analysis and retinal imaging with correlative histology. Exp Eye Res 2019;185:107683.Abstract
Tree shrews are small mammals with excellent vision and are closely related to primates. They have been used extensively as a model for studying refractive development, myopia, and central visual processing and are becoming an important model for vision research. Their cone dominant retina (∼95% cones) provides a potential avenue to create new damage/disease models of human macular pathology and to monitor progression or treatment response. To continue the development of the tree shrew as an animal model, we provide here the first measurements of higher order aberrations along with adaptive optics scanning light ophthalmoscopy (AOSLO) images of the photoreceptor mosaic in the tree shrew retina. To compare intra-animal in vivo and ex vivo cone density measurements, the AOSLO images were matched to whole-mount immunofluorescence microscopy. Analysis of the tree shrew wavefront indicated that the optics are well-matched to the sampling of the cone mosaic and is consistent with the suggestion that juvenile tree shrews are nearly emmetropic (slightly hyperopic). Compared with in vivo measurements, consistently higher cone density was measured ex vivo, likely due to tissue shrinkage during histological processing. Tree shrews also possess massive mitochondria ("megamitochondria") in their cone inner segments, providing a natural model to assess how mitochondrial size affects in vivo retinal imagery. Intra-animal in vivo and ex vivo axial distance measurements were made in the outer retina with optical coherence tomography (OCT) and transmission electron microscopy (TEM), respectively, to determine the origin of sub-cellular cone reflectivity seen on OCT. These results demonstrate that these megamitochondria create an additional hyper-reflective outer retinal reflective band in OCT images. The ability to use noninvasive retinal imaging in tree shrews supports development of this species as a model of cone disorders.
Siddiqui Y, Yin J. Anterior Segment Applications of Optical Coherence Tomography Angiography. Semin Ophthalmol 2019;:1-6.Abstract
: To review the current literature regarding optical coherence tomography angiography (OCT-A) applications in the anterior segment. : A literature search was performed for terms including OCT-Angiography, anterior segment, cornea, conjunctiva, iris, applications and use in ophthalmology. : Fifteen studies were identified, 14 in human subjects. Studies with OCT-A of the conjunctiva, episclera, cornea, and iris were identified, some with normal eyes imaged and others with various pathologies. Most of these studies imaged corneal neovascularization. Three studies described protocols used for image acquisition, one of which was referenced by two later papers. : OCT-A is a noninvasive technology with recent applications in the anterior segment. Several pilot studies have been performed on various anterior segment structures and disease states however standardization of image acquisition techniques is still needed. Future imaging could allow noninvasive and serial monitoring of pathology as well as recurrence after therapeutic intervention.
Werner AC, Shen LQ. A Review of OCT Angiography in Glaucoma. Semin Ophthalmol 2019;:1-8.Abstract
There is growing evidence that vascular dysfunction plays a role in the pathogenesis of glaucoma. The details of this relationship have remained elusive partially due to limitations in our ability to assess blood flow in the optic nerve. Optical coherence tomography angiography (OCTA) has emerged as a promising new technology well positioned to become the first clinically suitable test of optic nerve perfusion. OCTA uses the motion of red blood cells as an intrinsic contrast agent to create reproducible images of microvascular networks rapidly and non-invasively. A significant body of research regarding the use of OCTA in glaucoma has emerged in recent years. This review aims to provide an overview of the basic principles underlying OCTA technology, summarize the current literature regarding the application of OCTA in the management of glaucoma, and address the role of OCTA in explicating the vascular pathogenesis of glaucoma.
Sun P, Tandias RM, Yu G, Arroyo JG. SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS AND VISUAL OUTCOME AFTER TREATMENT FOR VITREOMACULAR TRACTION. Retina 2019;39(6):1054-1060.Abstract
PURPOSE: To evaluate the capacity of spectral domain optical coherence tomography macular findings to predict best-corrected visual acuity (BCVA) outcomes after treatment for symptomatic vitreomacular traction. METHODS: This consecutive, retrospective study included 24 patients (29 eyes) who experienced vitreomacular traction release with pneumatic vitreolysis (n = 9), intravitreal ocriplasmin (n = 6), or pars plana vitrectomy (n = 14). Preoperative and postoperative spectral domain optical coherence tomography images were used to determine the cone outer segment tips (COST) line, inner segment/outer segment line, and other frequently used features. Correlations between optical coherence tomography findings and BCVA were determined using regression analyses. RESULTS: Postoperative BCVA was correlated with length of the COST line and inner segment/outer segment line defects at 1, 3, 6, and 12 months postoperatively (P < 0.05) by simple linear regression analysis. However, multivariable regression analysis showed that only length of the COST line defect was significantly correlated with BCVA preoperatively and postoperatively (P < 0.05). Postoperative BCVA improvement at 12 months was significantly correlated with preoperative length of the COST line defect (P < 0.01). CONCLUSION: Recovery of the COST line and inner segment/outer segment line defects as observed by spectral domain optical coherence tomography is positively correlated with visual acuity improvement after successful vitreomacular traction treatment. Best-corrected visual acuity improvement may be predicted using the length of the preoperative COST line defect.
Gupta MP, Dow E, Jeng-Miller KW, Mukai S, Orlin A, Xu K, Yonekawa Y, Chan PRV. SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN COATS DISEASE. Retina 2019;39(6):1177-1185.Abstract
PURPOSE: To evaluate microstructural retinal abnormalities on spectral domain optical coherence tomography (SD-OCT) imaging of eyes with Coats disease. METHODS: This is a multicenter, retrospective study in which SD-OCT images of patients with treatment-naive Coats disease were correlated with clinical examination and visual acuity and, when available, followed longitudinally over time. RESULTS: Macular SD-OCT of 27 eyes with Coats disease revealed intraretinal edema (59%), intraretinal exudates (67%), subretinal fluid (37%), subretinal exudate (48%), ellipsoid zone disruption (52%), external limiting membrane disruption (41%), and subfoveal nodule (26%). All these microstructural abnormalities correlated with worse baseline and final visual acuities (P < 0.05) on univariate analysis, except for intraretinal edema which exhibited a nonstatistically significant trend toward worse baseline visual acuity (P = 0.16). Within stage 2b eyes, external limiting membrane disruption and subretinal nodule on SD-OCT were associated with worse baseline visual acuity (P = 0.02 for both), and there was a trend toward worse final visual acuity with external limiting membrane disruption and subretinal nodule (P = 0.17 for both) and worse baseline (P = 0.08) and final (P = 0.13) visual acuities with ellipsoid zone disruption. No microstructural abnormalities were noted on OCT of fellow eyes. CONCLUSION: Spectral domain OCT can identify microstructural abnormalities in Coats disease that are associated on univariate analysis with worse baseline visual acuity and visual prognosis. Further larger studies are necessary.
Gaier ED, Wang M, Gilbert AL, Rizzo JF, Cestari DM, Miller JB. Quantitative analysis of optical coherence tomographic angiography (OCT-A) in patients with non-arteritic anterior ischemic optic neuropathy (NAION) corresponds to visual function. PLoS One 2018;13(6):e0199793.Abstract
PURPOSE: Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common cause of non-glaucomatous optic neuropathy in older adults. Optical coherence tomographic angiography (OCT-A) is an emerging, non-invasive method to study the microvasculature of the posterior pole, including the optic nerve head. The goal of this study was to assess the vascular changes in the optic nerve head and peripapillary area associated with NAION using OCT-A. DESIGN: Retrospective comparative case series. METHODS: We performed OCT-A in 25 eyes (7 acute and 18 non-acute) in 19 patients with NAION. Fellow, unaffected eyes were analyzed for comparison. Patent macro- and microvascular densities were quantified in the papillary and peripapillary regions of unaffected, acutely affected, and non-acutely affected eyes and compared across these groups according to laminar segment and capillary sampling region, and with respect to performance on automated visual field testing. RESULTS: In acutely affected eyes, OCT-A revealed a reduction in the signal from the major retinal vessels and dilation of patent superficial capillaries in the peripapillary area. By contrast, non-acutely affected eyes showed attenuation of patent capillaries. The peripapillary choriocapillaris was obscured by edema in acute cases, but was similar between non-acute and unaffected eyes. The degree of dilation of the superficial microvasculature in the acute phase and attenuation in the non-acute phase each correlated inversely with visual field performance. The region of reduced patent capillary density correlated with the location of visual field defects in 80% of acute cases and 80% of non-acute cases. CONCLUSIONS: OCT-A reveals a dynamic shift in the superficial capillary network of the optic nerve head with strong functional correlates in both the acute and non-acute phases of NAION. Further study may validate OCT-A as a useful adjunctive diagnostic tool in the evaluation of ischemic optic neuropathy.
Ravindran K, Schmalz P, Torun N, Ronthal M, Chang Y-M, Thomas AJ. Angiographic Findings in the Tolosa-Hunt Syndrome and Resolution after Corticosteroid Treatment. Neuroophthalmology 2018;42(3):159-163.Abstract
The Tolosa-Hunt syndrome is a rare clinical condition characterized by painful opthalmoparesis associated with idiopathic granulomatous inflammation of the orbital apex and cavernous sinus. Historically, this condition was thought to result from arteritic changes in the internal carotid artery and cavernous sinus. Modern digital angiographic techniques were unavailable when THS was initially described, and few reports exist on its high-resolution angiographic findings. Painful ophthalmoparesis, especially of the oculomotor nerve, warrants vascular imaging because of the concern for an underlying aneurysm. Here, we describe angiographic findings of THS which may be useful for clinicians when encountering patients presenting with painful ophthalmoplegia.
Diaz DJ, Wang JC, Oellers P, Lains I, Sobrin L, Husain D, Miller JW, Vavvas DG, Miller JB. Imaging the Deep Choroidal Vasculature Using Spectral Domain and Swept Source Optical Coherence Tomography Angiography. J Vitreoretin Dis 2018;2(3):146-154.Abstract
Purpose: To evaluate the deeper choroidal vasculature in eyes with various ocular disorders using spectral domain (SD) optical coherence tomography angiography (OCTA) and swept source (SS) OCTA. Methods: Patients underwent OCTA imaging with either SD-OCTA (Zeiss Cirrus Angioplex or Optovue AngioVue) or SS-OCTA (Topcon Triton). Retinal pigment epithelium (RPE) integrity, structural visualization of deep choroidal vessels on en face imaging, and OCTA of deep choroidal blood flow signal were analyzed. Choroidal blood flow was deemed present if deeper choroidal vessels appeared bright after appropriate segmentation. Results: Structural visualization of choroidal vessels was feasible in all eyes by en face imaging. In both SD-OCTA and SS-OCTA, choroidal blood flow signal was present in all eyes with overlying RPE atrophy (100% of eyes with RPE atrophy, 28.6% of all imaged eyes, P < .001). Conclusions: While choroidal vessels can be visualized anatomically in all eyes by en face imaging, choroidal blood flow detection in deep choroidal vessel is largely restricted to areas with overlying RPE atrophy. Intact RPE acts as a barrier for reliable detection of choroidal flow using current OCTA technology, inhibiting evaluation of flow in deeper choroidal vessels in most eyes.
Yamaguchi M, Nakao S, Kaizu Y, Kobayashi Y, Nakama T, Arima M, Yoshida S, Oshima Y, Takeda A, Ikeda Y, Mukai S, Ishibashi T, Sonoda K-H. High-Resolution Imaging by Adaptive Optics Scanning Laser Ophthalmoscopy Reveals Two Morphologically Distinct Types of Retinal Hard Exudates. Sci Rep 2016;6:33574.Abstract

Histological studies from autopsy specimens have characterized hard exudates as a composition of lipid-laden macrophages or noncellular materials including lipid and proteinaceous substances (hyaline substances). However, the characteristics of hard exudates in living patients have not been examined due to insufficient resolution of existing equipment. In this study, we used adaptive optics scanning laser ophthalmoscopy (AO-SLO) to examine the characteristics of hard exudates in patients with retinal vascular diseases. High resolution imaging using AO-SLO enables morphological classification of retinal hard exudates into two types, which could not be distinguished either on fundus examination or by spectral domain optical coherence tomography (SD-OCT). One, termed a round type, consisted of an accumulation of spherical particles (average diameter of particles: 26.9 ± 4.4 μm). The other, termed an irregular type, comprised an irregularly shaped hyper-reflective deposition. The retinal thickness in regions with round hard exudates was significantly greater than the thickness in regions with irregular hard exudates (P = 0.01 →0.02). This differentiation of retinal hard exudates in patients by AO-SLO may help in understanding the pathogenesis and clinical prognosis of retinal vascular diseases.

Evans KK, Haygood TM, Cooper J, Culpan A-M, Wolfe JM. A half-second glimpse often lets radiologists identify breast cancer cases even when viewing the mammogram of the opposite breast. Proc Natl Acad Sci U S A 2016;113(37):10292-7.Abstract

Humans are very adept at extracting the "gist" of a scene in a fraction of a second. We have found that radiologists can discriminate normal from abnormal mammograms at above-chance levels after a half-second viewing (d' ∼ 1) but are at chance in localizing the abnormality. This pattern of results suggests that they are detecting a global signal of abnormality. What are the stimulus properties that might support this ability? We investigated the nature of the gist signal in four experiments by asking radiologists to make detection and localization responses about briefly presented mammograms in which the spatial frequency, symmetry, and/or size of the images was manipulated. We show that the signal is stronger in the higher spatial frequencies. Performance does not depend on detection of breaks in the normal symmetry of left and right breasts. Moreover, above-chance classification is possible using images from the normal breast of a patient with overt signs of cancer only in the other breast. Some signal is present in the portions of the parenchyma (breast tissue) that do not contain a lesion or that are in the contralateral breast. This signal does not appear to be a simple assessment of breast density but rather the detection of the abnormal gist may be based on a widely distributed image statistic, learned by experts. The finding that a global signal, related to disease, can be detected in parenchyma that does not contain a lesion has implications for improving breast cancer detection.

Deiner MS, Lietman TM, McLeod SD, Chodosh J, Porco TC. Surveillance Tools Emerging From Search Engines and Social Media Data for Determining Eye Disease Patterns. JAMA Ophthalmol 2016;134(9):1024-30.Abstract

IMPORTANCE: Internet-based search engine and social media data may provide a novel complementary source for better understanding the epidemiologic factors of infectious eye diseases, which could better inform eye health care and disease prevention. OBJECTIVE: To assess whether data from internet-based social media and search engines are associated with objective clinic-based diagnoses of conjunctivitis. DESIGN, SETTING, AND PARTICIPANTS: Data from encounters of 4143 patients diagnosed with conjunctivitis from June 3, 2012, to April 26, 2014, at the University of California San Francisco (UCSF) Medical Center, were analyzed using Spearman rank correlation of each weekly observation to compare demographics and seasonality of nonallergic conjunctivitis with allergic conjunctivitis. Data for patient encounters with diagnoses for glaucoma and influenza were also obtained for the same period and compared with conjunctivitis. Temporal patterns of Twitter and Google web search data, geolocated to the United States and associated with these clinical diagnoses, were compared with the clinical encounters. The a priori hypothesis was that weekly internet-based searches and social media posts about conjunctivitis may reflect the true weekly clinical occurrence of conjunctivitis. MAIN OUTCOMES AND MEASURES: Weekly total clinical diagnoses at UCSF of nonallergic conjunctivitis, allergic conjunctivitis, glaucoma, and influenza were compared using Spearman rank correlation with equivalent weekly data on Tweets related to disease or disease-related keyword searches obtained from Google Trends. RESULTS: Seasonality of clinical diagnoses of nonallergic conjunctivitis among the 4143 patients (2364 females [57.1%] and 1776 males [42.9%]) with 5816 conjunctivitis encounters at UCSF correlated strongly with results of Google searches in the United States for the term pink eye (ρ, 0.68 [95% CI, 0.52 to 0.78]; P < .001) and correlated moderately with Twitter results about pink eye (ρ, 0.38 [95% CI, 0.16 to 0.56]; P < .001) and with clinical diagnosis of influenza (ρ, 0.33 [95% CI, 0.12 to 0.49]; P < .001), but did not significantly correlate with seasonality of clinical diagnoses of allergic conjunctivitis diagnosis at UCSF (ρ, 0.21 [95% CI, -0.02 to 0.42]; P = .06) or with results of Google searches in the United States for the term eye allergy (ρ, 0.13 [95% CI, -0.06 to 0.32]; P = .19). Seasonality of clinical diagnoses of allergic conjunctivitis at UCSF correlated strongly with results of Google searches in the United States for the term eye allergy (ρ, 0.44 [95% CI, 0.24 to 0.60]; P < .001) and eye drops (ρ, 0.47 [95% CI, 0.27 to 0.62]; P < .001). CONCLUSIONS AND RELEVANCE: Internet-based search engine and social media data may reflect the occurrence of clinically diagnosed conjunctivitis, suggesting that these data sources can be leveraged to better understand the epidemiologic factors of conjunctivitis.

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