Imaging and Diagnostics

Imaging and Diagnostics Publications

Vujosevic S, Fantaguzzi F, Silva PS, Salongcay R, Brambilla M, Torti E, Nucci P, Peto T. Macula vs periphery in diabetic retinopathy: OCT-angiography and ultrawide field fluorescein angiography imaging of retinal non perfusion. Eye (Lond) 2024;Abstract
OBJECTIVES: To investigate the association between peripheral non-perfusion index (NPI) on ultrawide-field fluorescein angiography (UWF-FA) and quantitative OCT-Angiography (OCT-A) metrics in the macula. METHODS: In total, 48 eyes with UWF-colour fundus photos (CFP), UWF-FA (California, Optos) and OCT-A (Spectralis, Heidelberg) were included. OCT-A (3 × 3 mm) was used to determine foveal avascular zone (FAZ) parameters and vessel density (VD), perfusion density (PD), fractal dimension (FD) on superficial capillary plexus (SCP). NPI's extent and distribution was determined on UWF-FA within fovea centred concentric rings corresponding to posterior pole (<10 mm), mid-periphery (10-15 mm), and far-periphery (>15 mm) and within the total retinal area, the central macular field (6×6 mm), ETDRS fields and within each extended ETDRS field (P3-P7). RESULTS: Macular PD was correlated to NPI in total area of retina (Spearman ρ = 0.69, p < 0.05), posterior pole (ρ = 0.48, p < 0.05), mid-periphery (ρ = 0.65, p < 0.05), far-periphery (ρ = 0.59, p < 0.05), P3-P7 (ρ = 0,55 at least, p < 0.05 for each), central macula (ρ = 0.47, p < 0.05), total area in ETDRS (ρ = 0.55, p < 0.05). Macular VD and FD were correlated to NPI of total area of the retina (ρ = 0.60 and 0.61, p < 0.05), the mid-periphery (ρ = 0.56, p < 0.05) and far-periphery (ρ = 0.60 and ρ = 0.61, p < 0.05), and in P3-P7 (p < 0.05). FAZ perimeter was significantly corelated to NPI at posterior pole and central macular area (ρ = 0.37 and 0.36, p < 0.05), and FAZ area to NPI in central macular area (ρ = 0.36, p < 0.05). CONCLUSIONS: Perfusion macular metrics on OCT-A correlated with UWF-FA's non-perfusion (NP), particularly in the retina's mid and far periphery, suggesting that OCT-A might be a useful non-invasive method to estimate peripheral retinal NP.
Razavi P, Baldwin G, Garg I, Velazquez LM, Garcia M, Gan J, Choi H, Zeng R, Vingopoulos F, Husain D, Kim LA, Patel NA, Miller JB. Changes in wider field swept-source OCT angiography vascular metrics with anti-vascular endothelial growth factor therapy in central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 2024;Abstract
PURPOSE: To investigate the impact of anti-VEGF therapy on vascular metrics in eyes with macular edema secondary to central retinal vein occlusion (CRVO) using wider field swept-source OCT angiography (WF SS-OCTA). METHODS: We included 23 eyes with macular edema associated with non-ischemic CRVO from 22 patients treated with anti-VEGF therapy (median number of injections: 5 [2-9]). Changes in vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ) parameters were measured using WF SS-OCTA. Visual acuity (VA) and central subfield thickness (CST) were also measured. RESULTS: Median CST decreased significantly from 369 µm (305-531) to 267 µm (243-300, p < 0.001). VD and VSD parameters in 12 × 12 mm images showed significant reductions. For instance, VSD in the whole retina decreased from a median of 13.37 (11.22-13.74) to 11.29 (9.36-12.97, p = 0.013). Additionally, a significant increase in FAZ circularity was found, suggesting improved microvascular integrity. Significant inverse correlations were found between the number of anti-VEGF injections and all VSD and VD parameters on the 12 × 12 mm images (p < 0.05). Notably, the reductions in VSD and VD on 12 × 12 mm angiograms in the deep capillary plexus (DCP) after each injection significantly correlated with increased logMAR VA (worse VA). CONCLUSION: Anti-VEGF therapy in CRVO patients not only mitigates macular edema but also alters the overall microvascular morphology and functionality as revealed by WF SS-OCTA.
Silva PS, Zhang D, Jacoba CMP, Fickweiler W, Lewis D, Leitmeyer J, Curran K, Salongcay RP, Doan D, Ashraf M, Cavallerano JD, Sun JK, Peto T, Aiello LP. Automated Machine Learning for Predicting Diabetic Retinopathy Progression From Ultra-Widefield Retinal Images. JAMA Ophthalmol 2024;Abstract
IMPORTANCE: Machine learning (ML) algorithms have the potential to identify eyes with early diabetic retinopathy (DR) at increased risk for disease progression. OBJECTIVE: To create and validate automated ML models (autoML) for DR progression from ultra-widefield (UWF) retinal images. DESIGN, SETTING AND PARTICIPANTS: Deidentified UWF images with mild or moderate nonproliferative DR (NPDR) with 3 years of longitudinal follow-up retinal imaging or evidence of progression within 3 years were used to develop automated ML models for predicting DR progression in UWF images. All images were collected from a tertiary diabetes-specific medical center retinal image dataset. Data were collected from July to September 2022. EXPOSURE: Automated ML models were generated from baseline on-axis 200° UWF retinal images. Baseline retinal images were labeled for progression based on centralized reading center evaluation of baseline and follow-up images according to the clinical Early Treatment Diabetic Retinopathy Study severity scale. Images for model development were split 8-1-1 for training, optimization, and testing to detect 1 or more steps of DR progression. Validation was performed using a 328-image set from the same patient population not used in model development. MAIN OUTCOMES AND MEASURES: Area under the precision-recall curve (AUPRC), sensitivity, specificity, and accuracy. RESULTS: A total of 1179 deidentified UWF images with mild (380 [32.2%]) or moderate (799 [67.8%]) NPDR were included. DR progression was present in half of the training set (590 of 1179 [50.0%]). The model's AUPRC was 0.717 for baseline mild NPDR and 0.863 for moderate NPDR. On the validation set for eyes with mild NPDR, sensitivity was 0.72 (95% CI, 0.57-0.83), specificity was 0.63 (95% CI, 0.57-0.69), prevalence was 0.15 (95% CI, 0.12-0.20), and accuracy was 64.3%; for eyes with moderate NPDR, sensitivity was 0.80 (95% CI, 0.70-0.87), specificity was 0.72 (95% CI, 0.66-0.76), prevalence was 0.22 (95% CI, 0.19-0.27), and accuracy was 73.8%. In the validation set, 6 of 9 eyes (75%) with mild NPDR and 35 of 41 eyes (85%) with moderate NPDR progressed 2 steps or more were identified. All 4 eyes with mild NPDR that progressed within 6 months and 1 year were identified, and 8 of 9 (89%) and 17 of 20 (85%) with moderate NPDR that progressed within 6 months and 1 year, respectively, were identified. CONCLUSIONS AND RELEVANCE: This study demonstrates the accuracy and feasibility of automated ML models for identifying DR progression developed using UWF images, especially for prediction of 2-step or greater DR progression within 1 year. Potentially, the use of ML algorithms may refine the risk of disease progression and identify those at highest short-term risk, thus reducing costs and improving vision-related outcomes.
Szeto SK, Lai TYY, Vujosevic S, Sun JK, Sadda SR, Tan G, Sivaprasad S, Wong TY, Cheung CY. Optical coherence tomography in the management of diabetic macular oedema. Prog Retin Eye Res 2024;98:101220.Abstract
Diabetic macular oedema (DMO) is the major cause of visual impairment in people with diabetes. Optical coherence tomography (OCT) is now the most widely used modality to assess presence and severity of DMO. DMO is currently broadly classified based on the involvement to the central 1 mm of the macula into non-centre or centre involved DMO (CI-DMO) and DMO can occur with or without visual acuity (VA) loss. This classification forms the basis of management strategies of DMO. Despite years of research on quantitative and qualitative DMO related features assessed by OCT, these do not fully inform physicians of the prognosis and severity of DMO relative to visual function. Having said that, recent research on novel OCT biomarkers development and re-defined classification of DMO show better correlation with visual function and treatment response. This review summarises the current evidence of the association of OCT biomarkers in DMO management and its potential clinical importance in predicting VA and anatomical treatment response. The review also discusses some future directions in this field, such as the use of artificial intelligence to quantify and monitor OCT biomarkers and retinal fluid and identify phenotypes of DMO, and the need for standardisation and classification of OCT biomarkers to use in future clinical trials and clinical practice settings as prognostic markers and secondary treatment outcome measures in the management of DMO.
Kiely C, Douglas KA, Douglas VP, Miller JB, Lizano P. Overlap between ophthalmology and psychiatry - A narrative review focused on congenital and inherited conditions. Psychiatry Res 2024;331:115629.Abstract
A number of congenital and inherited diseases present with both ocular and psychiatric features. The genetic inheritance and phenotypic variants play a key role in disease severity. Early recognition of the signs and symptoms of those disorders is critical to earlier intervention and improved prognosis. Typically, the associations between these two medical subspecialties of ophthalmology and psychiatry are poorly understood by most practitioners so we hope to provide a narrative review to improve the identification and management of these disorders. We conducted a comprehensive review of the literature detailing the diseases with ophthalmic and psychiatric overlap that were more widely represented in the literature. Herein, we describe the clinical features, pathophysiology, molecular biology, diagnostic tests, and the most recent approaches for the treatment of these diseases. Recent studies have combined technologies for ocular and brain imaging such as optical coherence tomography (OCT) and functional imaging with genetic testing to identify the genetic basis for eye-brain connections. Additional work is needed to further explore these potential biomarkers. Overall, accurate, efficient, widely distributed and non-invasive tests that can help with early recognition of these diseases will improve the management of these patients using a multidisciplinary approach.
Kuo AN, Cortina MS, Greiner MA, Li JY, Miller DD, Shtein RM, Veldman PB, Yin J, Kim SJ, Shen JF. Advanced Corneal Imaging in Keratoconus: A Report by the American Academy of Ophthalmology. Ophthalmology 2024;131(1):107-121.Abstract
PURPOSE: To review the published literature on the diagnostic capabilities of the newest generation of corneal imaging devices for the identification of keratoconus. METHODS: Corneal imaging devices studied included tomographic platforms (Scheimpflug photography, OCT) and functional biomechanical devices (imaging an air impulse on the cornea). A literature search in the PubMed database for English language studies was last conducted in February 2023. The search yielded 469 citations, which were reviewed in abstract form. Of these, 147 were relevant to the assessment objectives and underwent full-text review. Forty-five articles met the criteria for inclusion and were assigned a level of evidence rating by the panel methodologist. Twenty-six articles were rated level II, and 19 articles were rated level III. There were no level I evidence studies of corneal imaging for the diagnosis of keratoconus found in the literature. To provide a common cross-study outcome measure, diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were extracted. (A perfect diagnostic test that identifies all cases properly has an AUC of 1.0.) RESULTS: For the detection of keratoconus, sensitivities for all devices and parameters (e.g., anterior or posterior corneal curvature, corneal thickness) ranged from 65% to 100%. The majority of studies and parameters had sensitivities greater than 90%. The AUCs ranged from 0.82 to 1.00, with the majority greater than 0.90. Combined indices that integrated multiple parameters had an AUC in the mid-0.90 range. Keratoconus suspect detection performance was lower with AUCs ranging from 0.66 to 0.99, but most devices and parameters had sensitivities less than 90%. CONCLUSIONS: Modern corneal imaging devices provide improved characterization of the cornea and are accurate in detecting keratoconus with high AUCs ranging from 0.82 to 1.00. The detection of keratoconus suspects is less accurate with AUCs ranging from 0.66 to 0.99. Parameters based on single anatomic locations had a wide range of AUCs. Studies with combined indices using more data and parameters consistently reported high AUCs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Wei Q, Wang X-Y, Zhang L-J, Yu C-Y, Shu H-Y, Liao X-L, Xu S-H, Su T, Kang M, Shao Y. A Functional Magnetic Resonance Imaging Study Using Dynamic Amplitude of Low-Frequency Fluctuation to Assess Brain Activity in Patients with Moyamoya Disease. Brain Connect 2023;13(10):621-630.Abstract
Introduction: The purpose of this study was to monitor and record the dynamic brain activity of patients with moyamoya disease (MMD), as well as to study the relationship between brain abnormalities and presenting clinical features. Methods: A total of 16 patients with MMD (2 males and 14 females) were invited to participate in the study, as were healthy controls (HCs) with the same number and sex ratio. In this study, the dynamic amplitude of low-frequency fluctuation (dALFF) was utilized to assess changes in spontaneous brain activity. Moreover, we also used correlation analysis to study the relationship among the measured mean of dALFF, behavioral performances, and the retinal nerve fiber layer and the Hospital Anxiety and Depression Scale (HADS) score to explore the potential relationship between MMD and anxiety and depression. Results: Our study reveals that in MMD, dALFF levels decreased in the left lingual gyrus, right insula, and occipital lobe. Discussion: In this study, we found and discussed the potential relationship between the abnormal activities in multiple brain regions and related functional network disorders in patients with MMD, as well as the damage to brain regions that process emotion and vision, in the hopes of providing more ideas for the clinical diagnosis and treatment of MMD.
Sayah DN, Garg I, Katz R, Zhu Y, Cui Y, Zeng R, Tandias R, Moon JY, Vingopoulos F, Wescott HE, Baldwin G, Wang K, Elze T, Ludwig CA, Vavvas DG, Miller JW, Husain D, Kim LA, Patel NA, Miller JB. Characterizing Macular Neovascularization in Myopic Macular Degeneration and Age-Related Macular Degeneration Using Swept Source OCTA. Clin Ophthalmol 2023;17:3855-3866.Abstract
PURPOSE: Visual prognosis and treatment burden for macular neovascularization (MNV) can differ between myopic macular degeneration (MMD) and age-related macular degeneration (AMD). We describe and compare MNV associated with MMD and AMD using swept-source (SS)-OCTA. PATIENTS AND METHODS: Adult patients with documented MNV associated with MMD or AMD were consecutively recruited. Qualitative and quantitative features were assessed from 6x6mm angiograms, including the MNV area and vessel density (VD). Descriptive statistics and linear regression analyses were carried out. RESULTS: Out of 75 enrolled eyes with diagnosed MNV (30 MMD-MNV and 45 AMD-MNV; mean age 55±19 and 75±8 years, respectively), 44 eyes had discernible MNV (11 MMD-MNV and 33 AMD-MNV) on SS-OCTA at the time of the study and were included in the analysis. The MMD-MNV group exhibited a three-fold smaller sized MNV (p=0.001), lower greatest linear dimension (p=0.009) and greatest vascular caliber (p<0.001) compared to AMD-MNVs, and had a higher prevalence of tree-in-bud pattern. Eyes with AMD showed a higher prevalence of type 1 MNVs with medusa pattern. There was no difference in the location of the MNV, shape's regularity, margins, presence of core vessel, capillary fringe, peripheral loops, or perilesional dark halo (p>0.05) between both conditions. After adjustment, decreased MNV area and increased VD were associated with the tree-in-bud pattern, whereas the diagnosis did not significantly influence those parameters. CONCLUSION: While larger studies are warranted, this study is the first to describe and compare MMD-MNV and AMD-MNV using SS-OCTA, providing relevant clinical insight on MNV secondary to MMD and AMD. These findings also further validate OCTA as a powerful tool to detect and characterize MNV non-invasively.
Lu ES, Cui Y, Le R, Zhu Y, Wang JC, Laíns I, Katz R, Lu Y, Zeng R, Garg I, Wu DM, Husain D, Kim LA, Miller JB. Widefield swept-source optical coherence tomography angiography metrics associated with neovascular glaucoma in patients with proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2023;Abstract
PURPOSE: To explore the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, including nonperfusion area (NPA) and neovascularization (NV), and presence of neovascular glaucoma (NVG) in patients with proliferative diabetic retinopathy (PDR). METHODS: A prospective, cross-sectional study was conducted from November 2018 to February 2020. A total of 85 eyes of 60 PDR patients without NVG and 9 eyes of 8 PDR patients with NVG were included. Retinal ischemic parameters (NPA; ischemia index [NPA/total retinal area]) and NV features (NV number; NV area; NV vessel density) were evaluated. Foveal avascular zone (FAZ), macular thickness/volume, and choroidal thickness/volume were obtained using the Zeiss ARI Network. WF SS-OCTA retinal and choroidal metrics, systemic, and ocular parameters were screened using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression for variable selection. Firth's bias-reduced logistic regression (outcome: presence of NVG) was subsequently used to identify parameters associated with NVG. RESULTS: After LASSO variable selection, 8 variables were significantly associated with the presence of NVG: DM duration (years), insulin (yes/no), best-corrected visual acuity (BCVA) (logMAR), IOP, ischemia index, skeletonized vessel density, macular thickness (inner inferior, outer temporal regions). Firth's bias-reduced logistic regression showed ischemia index (odds ratio [OR]=13.2, 95% confidence interval [CI]:5.3-30.7, P<0.001) and BCVA (OR=5.8, 95%CI:1.2-28.8, P<0.05) were associated with the presence of NVG. NV metrics, FAZ, and choroidal parameters were not related to NVG. CONCLUSIONS: Retinal ischemia but not NV was associated with the presence of NVG in patients with PDR using WF SS-OCTA. Larger, longitudinal studies are needed to validate imaging biomarkers associated with diabetic NVG.
Aiello LP, Jacoba CMP, Ashraf M, Cavallerano JD, Tolson AM, Tolls D, Sun JK, Silva PS. INTEGRATING MACULAR OPTICAL COHERENCE TOMOGRAPHY WITH ULTRAWIDE-FIELD IMAGING IN A DIABETIC RETINOPATHY TELEMEDICINE PROGRAM USING A SINGLE DEVICE. Retina 2023;43(11):1928-1935.Abstract
PURPOSE: To determine the effect of combined macular spectral-domain optical coherence tomography (SD-OCT) and ultrawide field retinal imaging (UWFI) within a telemedicine program. METHODS: Comparative cohort study of consecutive patients with both UWFI and SD-OCT. Ultrawide field retinal imaging and SD-OOCT were independently evaluated for diabetic macular edema (DME) and nondiabetic macular abnormality. Sensitivity and specificity were calculated with SD-OCT as the gold standard. RESULTS: Four hundred twenty-two eyes from 211 diabetic patients were evaluated. Diabetic macular edema severity by UWFI was as follows: no DME 93.4%, noncenter involved DME (nonciDME) 5.1%, ciDME 0.7%, ungradable DME 0.7%. SD-OCT was ungradable in 0.5%. Macular abnormality was identified in 34 (8.1%) eyes by UWFI and in 44 (10.4%) eyes by SD-OCT. Diabetic macular edema represented only 38.6% of referable macular abnormality identified by SD-OCT imaging. Sensitivity/specificity of UWFI compared with SD-OCT was 59%/96% for DME and 33%/99% for ciDME. Sensitivity/specificity of UWFI compared with SDOCT was 3%/98% for epiretinal membrane. CONCLUSION: Addition of SD-OCT increased the identification of macular abnormality by 29.4%. More than 58.3% of the eyes believed to have any DME on UWF imaging alone were false-positives by SD-OCT. The integration of SD-OCT with UWFI markedly increased detection and reduced false-positive assessments of DME and macular abnormality in a teleophthalmology program.
Blinder KJ, Calhoun C, Maguire MG, Glassman AR, Mein CE, Baskin DE, Vieyra G, Jampol LM, Chica MA, Sun JK, Martin DF, Martin DF. Home Optical Coherence Tomography Imaging for Newly Diagnosed Neovascular Age-Related Macular Degeneration: A Feasibility Study. Ophthalmol Retina 2023;Abstract
OBJECTIVE: To assess the feasibility of daily home optical coherence tomography (OCT) imaging among patients with neovascular age-related macular degeneration (nAMD). DESIGN: Prospective observational study. PARTICIPANTS: Participants with at least one eye with previously untreated nAMD and visual acuity 20/20 to 20/320. METHODS: Participants meeting the ocular eligibility criteria were considered for enrollment; those who provided consent received a Notal Vision Home OCT device. Participants were instructed to scan both eyes daily. Retina specialists managed treatment according to their standard practice, without access to the Home OCT data. The presence of fluid detected by a reading center from in-office OCT scans was compared to fluid volumes measured by the Notal OCT Analyzer (NOA) on Home OCT images. MAIN OUTCOME MEASURES: Proportion of participants meeting ocular eligibility criteria who participated in daily scanning, frequency and duration of scanning, proportion of scans eligible for fluid quantification, participant experience with the device, agreement between the reading center and NOA fluid determinations, and characteristics of fluid dynamics. RESULTS: Among 40 participants meeting ocular eligibility criteria, 14 (35%) initiated self-scanning. Planned travel (n=7, 17.5%) and patient-reported inadequate cell reception for the upload of images (n=5, 12.5%) were the most frequent reasons for not participating. Considering scans of the study eye only, the mean (SD) was 6.3 (0.6) for weekly scanning frequency and 47 (17) seconds for scan duration per eye. Among 2,304 scans, 86.5% were eligible for fluid quantification. All participants agreed that scanning became easier over time, and only one would not want to continue daily scanning. For 35 scan pairs judged as having fluid by in-office OCT, the NOA detected fluid on 31 scans (89%). For 14 scan pairs judged as having no fluid on in-office OCT, the NOA did not detect fluid on 10 scans (71%). Daily fluid patterns after treatment initiation varied considerably between patients. CONCLUSIONS: For patients with nAMD who initiated home scanning, frequency and quality of scanning and accuracy of fluid detection were sufficient to assess the monitoring of fluid at home. Accommodations for travel and Wi-Fi connectivity could improve uptake of the Home OCT device.
Seely KR, Freedman SF, Grace S, Weinert MC, Hong GJ, Toth CA, Grace Prakalapakorn S. Computer versus human-expert ranking of posterior pole vascular tortuosity and dilation using retinal vessel maps generated from bedside optical coherence tomography: a proof-of-concept study. J AAPOS 2023;27(6):351-354.Abstract
Semiautomated computer software (ie, ROPtool) can trace and analyze optical coherence tomography (OCT)-generated retinal vessel maps for plus/pre-plus disease with high reliability and accuracy. This proof-of-concept study found that ROPtool can reliably rank OCT-generated vessel maps for tortuosity and combined tortuosity/dilation, which correlated well with human-expert rankings and clinical examination.
Razavi P, Cakir B, Baldwin G, D'Amico DJ, Miller JB. Heads-Up Three-Dimensional Viewing Systems in Vitreoretinal Surgery: An Updated Perspective. Clin Ophthalmol 2023;17:2539-2552.Abstract
Three-Dimensional (3D) heads-up visualization systems have significantly advanced vitreoretinal surgery, providing enhanced detail and improved ergonomics. This review discusses the application of 3D systems in vitreoretinal surgery, their use in various procedures, their combination with other imaging modalities, and the role of this technology in medical education and telementoring. Furthermore, the review highlights the benefits of 3D systems, such as improved ergonomics, reduced phototoxicity, enhanced depth of field, and the use of color filters. Potential challenges, including the learning curve and additional costs, are also addressed. The review concludes by exploring promising future applications, including teleophthalmology for remote assistance and specialist availability expansion, virtual reality integration for global clinical education, and the combination of remotely robotic-guided surgery with artificial intelligence for precise, efficient surgical procedures. This comprehensive review offers insights into the current state and future potential of 3D heads-up visualization systems in vitreoretinal surgery, underscoring the transformative impact of this technology on ophthalmology.

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