Imaging and Diagnostics

Imaging and Diagnostics Publications

Cui Y, Zhu Y, Lu ES, Le R, Laíns I, Katz R, Wang JC, Garg I, Lu Y, Zeng R, Eliott D, Vavvas DG, Husain D, Miller JW, Kim LA, Wu DM, Miller JB. Widefield Swept-Source OCT Angiography Metrics Associated with the Development of Diabetic Vitreous Hemorrhage: A Prospective Study. Ophthalmology 2021;128(9):1312-1324.Abstract
PURPOSE: To investigate the association among widefield swept-source (SS) OCT angiography (OCTA) metrics and systemic parameters and vitreous hemorrhage (VH) occurrence in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-five eyes from 45 adults with PDR, with no history of VH, followed up for at least 3 months. METHODS: All patients underwent widefield SS OCTA (Montage 15 × 15 mm and high-definition (HD)-51 line scan) imaging. Images were evaluated independently by 2 graders for quantitative and qualitative widefield SS OCTA metrics defined a priori. Systemic and ocular parameters and widefield SS OCTA metrics were screened using least absolute shrinkage and selection operator and logistic or Cox regression for variable selection. Firth's bias-reduced logistic regression models (outcome, occurrence of VH) and Cox regression models (outcome, time to occurrence of VH) were used to identify parameters associated with VH occurrence. MAIN OUTCOME MEASURES: Occurrence of VH. RESULTS: Over a median follow-up of 363 days (range, 28-710 days), 13 of 55 PDR eyes (24%) demonstrated VH during the follow-up period. Presence of extensive neovascularizations (odds ratio, 8.05; 95% confidence interval [CI], 1.43-58.56; P = 0.02), defined as neovascularizations with total area of more than 4 disc diameters, and forward neovascularizations (odds ratio, 5.42; 95% CI, 1.26-35.16; P = 0.02) that traversed the posterior hyaloid face into the vitreous were associated with the occurrence of VH. The presence of flat neovascularizations (odds ratio, 0.25; 95% CI, 0.04-1.01; P = 0.05) confined to the posterior hyaloid face was associated with a lower risk of VH with borderline significance. Similarly, presence of extensive neovascularizations (hazard ratio, 18.24; 95% CI, 3.51-119.47; P < 0.001) and forward neovascularizations (hazard ratio, 9.60; 95% CI, 2.07-68.08; P = 0.002) was associated significantly with time to development of VH. CONCLUSIONS: Widefield SS OCTA is useful for evaluating neovascularizations and their relationship with the vitreous. The presence of forward and extensive neovascularizations was associated with the occurrence of VH in patients with PDR. Larger samples and longer follow-up are needed to verify the risk factors and imaging biomarkers for diabetic VH.
Moon JY, Garg I, Cui Y, Katz R, Zhu Y, Le R, Lu Y, Lu ES, Ludwig CA, Elze T, Wu DM, Eliott D, Miller JW, Kim LA, Husain D, Vavvas DG, Miller JB. Wide-field swept-source optical coherence tomography angiography in the assessment of retinal microvasculature and choroidal thickness in patients with myopia. Br J Ophthalmol 2021;Abstract
BACKGROUND/AIMS: Pathological myopia (PM) is a leading cause of blindness worldwide. We aimed to evaluate microvascular and chorioretinal changes in different stages of myopia with wide-field (WF) swept-source (SS) optical coherence tomography angiography (OCTA). METHODS: This prospective cross-sectional observational study included 186 eyes of 122 patients who had undergone imaging between November 2018 and October 2020. Vessel density (VD) and vessel skeletonised density (VSD) of superficial capillary plexus, deep capillary plexus and whole retina, as well as foveal avascular zone parameters, retinal thickness (RT) and choroidal thickness (CT), were calculated. RESULTS: This study evaluated 75 eyes of 48 patients with high myopia (HM), 43 eyes of 31 patients with mild to moderate myopia and 68 eyes of 53 age-matched controls. Controlling for age and the presence of systemic hypertension, we found that HM was associated with decrease in VD and VSD in all layers on 12×12 mm² scans. Furthermore, HM was associated with a VD and VSD decrease in every Early Treatment Diabetic Retinopathy Study grid, with a larger decrease temporally (βVD=-0.39, βVSD=-10.25, p<0.01). HM was associated with decreased RT and CT. Reduction in RT was outside the macular region, while reduction in CT was in the macular region. CONCLUSION: Using WF SS-OCTA, we identified reduction in microvasculature and structural changes associated with myopia. Decrease in VD and VSD was greater in the temporal quadrant, and reductions in RT and CT were uneven across the retina. Further work may help identify risk factors for the progression of PM and associated vision-threatening complications.
Bosque LE, Yamarino CR, Salcedo N, Schneier AJ, Gold RS, Blumenfeld LC, Hunter DG. Evaluation of the blinq vision scanner for detection of amblyopia and strabismus. J AAPOS 2021;Abstract
PURPOSE: To report the results of a clinical study designed to evaluate the accuracy of the blinq pediatric vision scanner, which detects amblyopia and strabismus directly by means of retinal polarization scanning, unlike other vision screening devices, which infer possible disease based on detection of refractive risk factors. METHODS: Subjects 1-20 years of age were prospectively enrolled in this cross-sectional diagnostic accuracy study with planned enrollment of 200. All enrolled subjects were tested by individuals masked to the diagnosis, followed by complete ophthalmologic examination by pediatric ophthalmologists masked to the screening result. Patients previously treated for amblyopia or strabismus were analyzed separately. RESULTS: The study cohort comprised 193 subjects, 53 of whom had been previously treated, leaving 140 treatment-naïve subjects, including 65 (46%) with amblyopia or strabismus, 11 (8%) with risk factors/suspected binocular vision deficit without amblyopia/strabismus, and 64 (46%) controls. Sensitivity was 100%, with all 66 patients with referral-warranted ocular disease referred. Five patients with intermittent strabismus receiving pass results were deemed "acceptable pass" when considering patient risk factors and amblyogenic potential. Specificity was 91%, with 7 incorrect referrals. Subanalysis of children aged 2-8 years (n = 92) provided similar results (sensitivity 100%; specificity 89%). CONCLUSIONS: In this study cohort, the blinq showed very high sensitivity and specificity for detecting referral-warranted amblyopia and strabismus. Implementation of the device in vision screening programs could lead to improved rates of disease detection and reduction in false referrals.
Currant H, Hysi P, Fitzgerald TW, Gharahkhani P, Bonnemaijer PWM, Senabouth A, Hewitt AW, and Consortium UKBEV, and Consortium UKBEV, Atan D, Aung T, Charng J, Choquet H, Craig J, Khaw PT, Klaver CCW, Kubo M, Ong J-S, Pasquale LR, Reisman CA, Daniszewski M, Powell JE, Pébay A, Simcoe MJ, Thiadens AAHJ, van Duijn CM, Yazar S, Jorgenson E, Macgregor S, Hammond CJ, Mackey DA, Wiggs JL, Foster PJ, Patel PJ, Birney E, Khawaja AP. Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images. PLoS Genet 2021;17(5):e1009497.Abstract
Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
da Cunha LP, Cavalcante Costa MAA, de Miranda HA, Reis Guimarães J, Aihara T, Ludwig CA, Rosenblatt T, Callaway NF, Pasricha M, Al-Moujahed A, Vail D, Ji MH, Kumm J, Moshfeghi DM. Comparison between wide-field digital imaging system and the red reflex test for universal newborn eye screening in Brazil. Acta Ophthalmol 2021;Abstract
PURPOSE: To compare neonatal eye screening using the red reflex test (RRT) versus the wide-field digital imaging (WFDI) system. METHODS: Prospective cohort study. Newborns (n = 380, 760 eyes) in the Maternity Ward of Irmandade Santa Casa de Misericórdia de São Paulo hospital from May to July 2014 underwent RRT by a paediatrician and WFDI performed by the authors. Wide-field digital imaging (WFDI) images were analysed by the authors. Validity of the paediatrician's RRT was assessed by unweighted kappa [κ] statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: While WFDI showed abnormalities in 130 eyes (17.1%), RRT was only abnormal in 13 eyes (1.7%). Wide-field digital imaging (WFDI) detected treatable retina pathology that RRT missed including hyphema, CMV retinitis, FEVR and a vitreous haemorrhage. The sensitivity of the paediatrician's RRT to detect abnormalities was poor at 0.77% (95% confidence interval, CI, 0.02%-4.21%) with a PPV of only 7.69% (95% CI, 1.08%-38.85%). Overall, there was no agreement between screening modalities (κ = -0.02, 95% CI, -0.05 to 0.01). The number needed to screen to detect ocular abnormalities using WFDI was 5.9 newborns and to detect treatable abnormalities was 76 newborns. CONCLUSION: While RRT detects gross abnormalities that preclude visualization of the retina (i.e. media opacities and very large tumours), only WFDI consistently detects subtle treatable retina and optic nerve pathology. With a higher sensitivity than the current gold standard, universal WFDI allows for early detection and management of potentially blinding ophthalmic disease missed by RRT.
Schill HM, Wolfe JM, Brady TF. Relationships between expertise and distinctiveness: Abnormal medical images lead to enhanced memory performance only in experts. Mem Cognit 2021;49(6):1067-1081.Abstract
Memories are encoded in a manner that depends on our knowledge and expectations ("schemas"). Consistent with this, expertise tends to improve memory: Experts have elaborated schemas in their domains of expertise, allowing them to efficiently represent information in this domain (e.g., chess experts have enhanced memory for realistic chess layouts). On the other hand, in most situations, people tend to remember abnormal or surprising items best-those that are also rare or out-of-the-ordinary occurrences (e.g., surprising-but not random-chess board configurations). This occurs, in part, because such images are distinctive relative to other images. In the current work, we ask how these factors interact in a particularly interesting case-the domain of radiology, where experts actively search for abnormalities. Abnormality in mammograms is typically focal but can be perceived in the global "gist" of the image. We ask whether, relative to novices, expert radiologists show improved memory for mammograms. We also test for any additional advantage for abnormal mammograms that can be thought of as unexpected or rare stimuli in screening. We find that experts have enhanced memory for focally abnormal images relative to normal images. However, radiologists showed no memory benefit for images of the breast that were not focally abnormal, but were only abnormal in their gist. Our results speak to the role of schemas and abnormality in expertise; the necessity for spatially localized abnormalities versus abnormalities in the gist in enhancing memory; and the nature of memory and decision-making in radiologists.
Hanumunthadu D, Lescrauwaet B, Jaffe M, Sadda SV, Wiecek E, Hubschman JP, Patel PJ. Clinical Update on Metamorphopsia: Epidemiology, Diagnosis and Imaging. Curr Eye Res 2021;:1-15.Abstract
Purpose: To discuss the pathophysiology of metamorphopsia, its characterisation using retinal imaging and methods of assessment of patient symptoms and visual function.Methods: A literature search of electronic databases was performedResults: Metamorphopsia has commonly been associated with vitreomacular interface disorders (such as epiretinal membrane) and has also regularly been noted in diseases of the retina and choroid, particularly age-related macular degeneration and central serous chorioretinopathy. Developments in optical coherence tomography retinal imaging have enabled improved imaging of the foveal microstructure and have led to the localisation of the pathophysiology of metamorphopsia within the retinal layers of the macula. Alteration of alignment of inner and outer retinal layers at various retinal loci has been identified using multimodal imaging in patients with metamorphopsia in a range of conditions. Although the Amsler Grid assessment of metamorphopsia is a useful clinical indicator, new emerging methods of metamorphopsia assessment with psychophysical tests such as M-CHARTS and preferential hyperacuity perimetry, have been developed.Conclusions: It appears that there is a complex relationship between visual acuity and metamorphopsia symptoms that vary between retinal conditions. Although metamorphopsia has traditionally been challenging to measure in the clinic, advances in technology promise more robust, easy-to-use tests. It is possible that home assessment of metamorphopsia, particularly in conditions such as age-related macular degeneration, may help to guide the need for further clinic evaluation and consideration of treatment.
Jabroun MN, AlWattar BK, Fulton AB. Optical Coherence Tomography Angiography in Prematurity. Semin Ophthalmol 2021;36(4):264-269.Abstract
Purpose: During normal foveal development there is a close interaction between the neurosensory and vascular elements of the fovea making it vulnerable to prematurity and retinopathy of prematurity (ROP). We aim to assess this potential effect on foveal development in preterms evaluated simultaneously with both optical coherence tomography (OCT) and OCT angiography (OCTA).Method: Unrestricted literature search in the PubMed and Cochrane library databases yielded 20 distinct citations. Fifteen were relevant and reviewed.Results: In preterms, OCTA demonstrated a significant decrease in the foveal avascular zone area and an increase in foveal vessel density. OCT showed a decrease in foveal pit depth and an increase in the thickness of the subfoveal retinal layers. Some studies correlated these changes with reduced vision.Conclusion: Changes in the vascular and neurosensory retina were found in premature children. It remains unclear whether this is related to prematurity alone or ROP and its treatment.
Rageh A, Ashraf M, Fleming A, Silva PS. Automated Microaneurysm Counts on Ultrawide Field Color and Fluorescein Angiography Images. Semin Ophthalmol 2021;36(4):315-321.Abstract
BACKGROUND: The severity and extent of microaneurysms (MAs) have been used to determine diabetic retinopathy (DR) severity and estimate the risk of DR progression over time. The recent introduction of ultrawide field (UWF) imaging has allowed ophthalmologists to readily image nearly the entire retina. Manual counting of MAs, especially on UWF images, is laborious and time-consuming, limiting its potential use in clinical settings. Automated MA counting techniques are potentially more accurate and reproducible compared to manual methods. METHOD: Review of available literature on current techniques of automated MA counting techniques on both ultrawide field (UWF) color images (CI) and fluorescein angiography (FA) images. RESULTS: Automated MA counting techniques on UWF images are still in the early phases of development with UWF-FA counts being further along. Early studies have demonstrated that these techniques are accurate and reproducible. CONCLUSION: Automated techniques may be an appropriate option for detecting and quantifying MAs on UWF images, especially in eyes with earlier DR severity. Larger studies are needed to appropriately validate these techniques and determine if they add substantially to clinical practice compared to standard DR grading.
Wang M, Garg I, Miller JB. Wide Field Swept Source Optical Coherence Tomography Angiography for the Evaluation of Proliferative Diabetic Retinopathy and Associated Lesions: A Review. Semin Ophthalmol 2021;36(4):162-167.Abstract
Retinal imaging remains the mainstay for monitoring and grading diabetic retinopathy. The gold standard for detecting proliferative diabetic retinopathy (PDR) requiring treatment has long been the seven-field stereoscopic fundus photography and fluorescein angiography. In the past decade, ultra-wide field fluorescein angiography (UWF-FA) has become more commonly used in clinical practice for the evaluation of more advanced diabetic retinopathy. Since its invention, optical coherence tomography (OCT) has been an important tool for the assessment of diabetic macular edema; however, OCT offered little in the assessment of neovascular changes associated with PDR until OCT-A became available. More recently, swept source OCT allowed larger field of view scans to assess a variety of DR lesions with wide field swept source optical coherence tomography (WF-SS-OCTA). This paper reviews the role of WF-SS-OCTA in detecting neovascularization of the disc (NVD), and elsewhere (NVE), microaneurysms, changes of the foveal avascular zone (FAZ), intraretinal microvascular abnormalities (IRMA), and capillary non-perfusion, as well as limitations of this evolving technology.
Dahrouj M, Miller JB. Artificial Intelligence (AI) and Retinal Optical Coherence Tomography (OCT). Semin Ophthalmol 2021;36(4):341-345.Abstract
Ophthalmology has been at the forefront of medical specialties adopting artificial intelligence. This is primarily due to the "image-centric" nature of the field. Thanks to the abundance of patients' OCT scans, analysis of OCT imaging has greatly benefited from artificial intelligence to expand patient screening and facilitate clinical decision-making.In this review, we define the concepts of artificial intelligence, machine learning, and deep learning and how different artificial intelligence algorithms have been applied in OCT image analysis for disease screening, diagnosis, management, and prognosis.Finally, we address some of the challenges and limitations that might affect the incorporation of artificial intelligence in ophthalmology. These limitations mainly revolve around the quality and accuracy of datasets used in the algorithms and their generalizability, false negatives, and the cultural challenges around the adoption of the technology.
Armstrong GW, Kalra G, De Arrigunaga S, Friedman DS, Lorch AC. Anterior Segment Imaging Devices in Ophthalmic Telemedicine. Semin Ophthalmol 2021;36(4):149-156.Abstract
Obtaining a clear assessment of the anterior segment is critical for disease diagnosis and management in ophthalmic telemedicine. The anterior segment can be imaged with slit lamp cameras, robotic remote controlled slit lamps, cell phones, cell phone adapters, digital cameras, and webcams, all of which can enable remote care. The ability of these devices to identify various ophthalmic diseases has been studied, including cataracts, as well as abnormalities of the ocular adnexa, cornea, and anterior chamber. This article reviews the current state of anterior segment imaging for the purpose of ophthalmic telemedical care.
Ludwig CA, Moon J, Garg I, Miller JB. Ultra-Widefield Imaging for Evaluation of the Myopic Eye. Semin Ophthalmol 2021;36(4):185-190.Abstract
Topic : Ultra-widefield (UWF) imaging of the myopic eye. Clinical Relevance : Myopes, and particularly high and pathologic myopes, present a unique challenge in fundoscopic imaging. Critical pathology is often located in the anteriormost portion of the retina, variations in posterior segment contour are difficult to capture in two-dimensional images, and extremes in axial length make simply focusing imaging devices difficult. Methods: We review the evolution of modalities for ophthalmic imaging (color fundus photography [CFP], optical coherence topography [OCT], angiography, artificial intelligence [AI]) to present day UWF technology and its impact on our understanding of myopia. Results: Advances in UWF technology address many of the challenges in fundoscopic imaging of myopes, providing new insights into the structure and function of the myopic eye. UWF CFP improves our ability to detect and document anterior peripheral pathology prevalent in approximately half of all high myopes. UWF OCT better captures the staphylomatous contour of the myopic eye, providing enhanced visualization of the vitreoretinal interface and progressive development of myopic traction maculopathy. UWF angiography highlights the posterior vortex veins, thin choriocapillaris, far peripheral avascularity, and peripheral retinal capillary microaneurysms more prevalent in the myopic eye. Researchers have demonstrated the ability of AI algorithms to predict refractive error, and great potential remains in the use of AI technology for the screening and prevention of myopic disease. Conclusion: We note significant progress in our ability to capture anterior pathology and improved image quality of the posterior segment of high and pathologic myopes. The next jump forward for UWF imaging will be the ability to capture a high quality ora to ora multimodal fundoscopic image in a single scan that will allow for sensitive AI-assisted screening of myopic disease.

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