Imaging and Diagnostics

Imaging and Diagnostics Publications

Le R, Cui Y, Lu ES, Zhu Y, Garg I, Wang JC, Lu Y, Zeng R, Katz R, Laíns I, Eliott D, Husain D, Kim LA, Miller JB. Prevalence of venous loops and association with retinal ischemia in diabetic retinopathy using widefield swept-source OCT angiography. Graefes Arch Clin Exp Ophthalmol 2023;Abstract
PURPOSE: To investigate the prevalence and clinical characteristics of diabetic patients with retinal venous loops (RVLs) and to assess the association with retinal ischemia using widefield swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: In this retrospective, cross-sectional study, a total of 195 eyes of 132 diabetic patients (31 eyes with no diabetic retinopathy (DR), 76 eyes with nonproliferative DR (NPDR), and 88 eyes with proliferative DR (PDR)) were imaged with WF SS-OCTA using Angio 6 × 6 mm and Montage 15 × 15 mm scans. Quantitative ischemia-related parameters, including ischemia index (ratio of nonperfusion area to total retinal area), foveal avascular zone (FAZ), and neovascularization features, were evaluated. RVLs were classified as type I or type II according to the branching level of the feeder vessel. A multivariate generalized estimating equations (GEE) logistic regression model was used to analyze the association of systemic parameters and ischemia-related metrics with RVLs in PDR eyes. RESULTS: Forty-eight RVLs were identified in 22 eyes (11.28%). The prevalence of RVLs was higher in PDR compared to NPDR eyes (21.59% vs. 3.95%, P < 0.05). Type II RVLs accounted for a higher proportion than type I (89.58% vs. 10.42%, P < 0.001). RVLs were more likely to originate from superior (vs. inferior) and temporal (vs. nasal) veins (P < 0.05). The GEE model showed that neovascularization (NV) flow area and diastolic blood pressure were associated with RVLs in the PDR group (P < 0.05). CONCLUSION: WF SS-OCTA is useful for the identification of RVLs in patients with DR. NV flow area and diastolic blood pressure were associated with the presence of RVLs in eyes with PDR. Ischemia index, FAZ, and other WF SS-OCTA parameters were not associated with RVLs. Further longitudinal studies are needed to identify the role of RVLs in DR progression.
Munsell MK, Garg I, Duich M, Zeng R, Baldwin G, Wescott HE, Koch T, Wang KL, Patel NA, Miller JB. A normative database of wide-field swept-source optical coherence tomography angiography quantitative metrics in a large cohort of healthy adults. Graefes Arch Clin Exp Ophthalmol 2023;Abstract
PURPOSE: Data from healthy eyes is needed to interpret optical coherence tomography angiography (OCTA) findings. However, very little normative data is available for wide-field swept-source OCTA (WF SS-OCTA), particularly 12 × 12-mm and disc-centered angiograms. Therefore, we aim to report quantitative metrics in a large sample of control eyes. METHODS: In this cross-sectional observational study, 482 eyes of 375 healthy adults were imaged on the 100 kHz Zeiss PLEX® Elite 9000 using protocols centered on the fovea (3 × 3, 6 × 6, and 12 × 12-mm) and optic disc (6 × 6 and 12 × 12-mm) between December 2018 and January 2022. The ARI Network (Zeiss Portal v5.4) was used to calculate vessel density (VD) and vessel skeletonized density (VSD) in the superficial capillary plexus, deep capillary plexus, and whole retina, as well as foveal avascular zone (FAZ) parameters. Mixed-effect multiple linear regression models were used for statistical analysis. RESULTS: The subjects' median age was 55 (38-63) years, and 201 (53.6%) were female. Greater age and worse best-corrected visual acuity (BCVA) were associated with significantly lower VD and VSD (p < 0.05). VD and VSD differed based on race and cataract status, but not sex, on some scan protocols (p < 0.05). FAZ circularity decreased with age, and FAZ dimensions differed based on race and ethnicity in certain scan protocols. CONCLUSIONS: We report a large database of parafoveal and peripapillary vascular metrics in several angiogram sizes. In referencing these values, researchers must consider characteristics such as age, race, and BCVA, but will have a valuable point of comparison for OCTA measurements in pathologic settings.
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 2023;107(1):102-108.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.
Rudnick ND, Vingopoulos F, Wang JC, Garg I, Cui Y, Zhu Y, Le R, Katz R, Lu Y, Patel NA, Miller JB. Characterising collateral vessels in eyes with branch retinal vein occlusions using widefield swept-source optical coherence tomography angiography. Br J Ophthalmol 2022;Abstract
BACKGROUND/AIMS: To characterise the morphology, location and functional significance of both macular and extramacular collateral vessels (CVs) in patients with a history of branch retinal vein occlusion (BRVO) using widefield swept-source optical coherence tomography angiography (WF SS OCTA). METHODS: Patients with a history of BRVO underwent WF SS OCTA testing to acquire 12×12 mm images, which were evaluated for CVs and non-perfusion area (NPA). Region of interest analysis of individual CVs was performed to identify correlations between CV size, depth and retinal location. Mixed effects multivariate regression analyses of factors associated with NPA and visual acuity (VA) were performed. RESULTS: Fifty-five CVs were identified in 28 BRVO eyes from 27 patients. CVs were identified in 42.9% (12/28) of eyes with a history of BRVO, and of these, 45.5% (25/55) were extramacular. The majority of CVs (87.3%, 48/55) coursed through both the superficial and the deep capillary plexus (DCP), while a subset (12.7%, 7/55) were strictly superficial. No CVs were found to course strictly through the DCP alone. CV depth increased with distance from the optic disc (p=0.011) and CV size increased with distance from the fovea (p=0.005). There were no statistically significant associations between CVs and NPA, or between CVs and VA. CONCLUSIONS: WF SS OCTA revealed that a large fraction of CVs that form after BRVO are extramacular, and the morphology of CVs varies as a function of retinal location. Depth-resolved study of CVs may offer valuable insights on the pathophysiological mechanisms leading to the development of macular oedema.
Houston KE, Paschalis EI. Feasibility of Magnetic Levator Prosthesis Frame Customization Using Craniofacial Scans and 3-D Printing. Transl Vis Sci Technol 2022;11(10):34.Abstract
Purpose: To determine the feasibility of a custom frame generation approach for nonsurgical management of severe blepharoptosis with the magnetic levator prosthesis (MLP). Methods: Participants (n = 8) with severe blepharoptosis (obscuring the visual axis) in one or both eyes who had previously been using a non-custom MLP had a craniofacial scan with a smartphone app to generate a custom MLP frame. A magnetic adhesive was attached to the affected eyelid. The custom MLP frame held a cylindrical magnet near the eyebrow above the affected eyelid, suspending it in the magnetic field while still allowing blinking. The spectacle magnet could be rotated manually, providing adjustable force via angular translation of the magnetic field. Fitting success and comfort were recorded, and interpalpebral fissure (IPF) was measured from video frames after 20 minutes in-office and one-week at-home use. Preference was documented, custom versus non-custom. Results: Overall, 88% of patients (7/8) were successfully fitted with a median 9/10 comfort (interquartile 7-10) and median ptosis improvement of 2.3 mm (1.3-5.0); P = 0.01). Exact binomial testing suggested, with 80% power, that the true population success rate was significantly greater than 45% (P = 0.05). Five participants took the custom MLP home for one week, with only one case of mild conjunctival redness which resolved without treatment. Highest to lowest force modulation resulted in a marginally significant median IPF adjustment of 1.5 mm (0.8 to 2.7; P = 0.06). All preferred the custom frame. Conclusions: The three-dimensional custom MLP frame generation approach using a smartphone app-based craniofacial scan is a feasible approach for clinical deployment of the MLP. Translational Relevance: First demonstration of customized frame generation for the MLP.
Choudhury A, Reyes N, Galor A, Mehra D, Felix E, Moulton EA. Clinical neuroimaging of photophobia in individuals with chronic ocular surface pain. Am J Ophthalmol 2022;Abstract
PURPOSE: To examine neural mechanisms underlying photophobia in individuals with chronic ocular surface pain using functional magnetic resonance imaging (fMRI). DESIGN: Cross-sectional case/control analysis METHODS: 16 subjects from the Miami Veterans Affairs eye clinic underwent comprehensive ocular surface evaluations and were surveyed for ocular surface symptoms. Cases included subjects who reported chronic ocular surface pain symptoms and light sensitivity at least most of the time over one week. Controls included subjects without chronic ocular surface pain who reported no or minimal light sensitivity. All subjects viewed light stimuli during two fMRI scans, one before and one after topical anesthetic instillation, and rated their level of pain intensity to the stimulus at the end of each scan. Areas of brain activation in response to light stimuli presentation were correlated to pain responses and examined post- vs. pre-anesthesia. RESULTS: Cases (n=8) reported higher pain intensity ratings than controls (n=8) in response to light stimuli during fMRI. Case ratings correlated more with light-evoked activation in pain-related areas within the trigeminal brainstem, primary somatosensory cortex (S1), anterior mid-cingulate cortex (aMCC), and insula than with controls. Topical anesthesia led to varying responses in pain ratings among cases as well as decreased light-evoked activation in S1 and aMCC. CONCLUSIONS: The trigeminal nociceptive system may contribute to photophobia in individuals with chronic ocular surface pain. We demonstrate modulation of cortical structures in this pathway with topically applied anesthetic to the eyes. Further understanding of modulatory interactions that govern ocular surface pain and photophobia is critical for developing effective, precision-based therapies.
Singh RB, Perepelkina T, Testi I, Young BK, Mirza T, Invernizzi A, Biswas J, Agarwal A. Imaging-based Assessment of Choriocapillaris: A Comprehensive Review. Semin Ophthalmol 2022;:1-22.Abstract
PURPOSE: Over the past two decades, advancements in imaging modalities have significantly evolved the diagnosis and management of retinal diseases. Through these novel platforms, we have developed a deeper understanding of the anatomy of the choroidal vasculature and the choriocapillaris. The recently developed tools such as optical coherence tomography (OCT) and OCT angiography (OCTA) have helped elucidate the pathological mechanisms of several posterior segment diseases. In this review, we have explained the anatomy of the choriocapillaris and its close relationship to the outer retina and retinal pigment epithelium. METHODS: A comprehensive search of medical literature was performed through the Medline/PubMed database using search terms: choriocapillaris, choroid, quantification, biomarkers, diabetic retinopathy, age-related macular degeneration, choroidal blood flow, mean blur rate, flow deficit, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, indocyanine green angiography, OCTA, Doppler imaging, uveitis, choroiditis, white dot syndrome, tubercular serpiginous-like choroiditis, choroidal granuloma, pachychoroid, toxoplasmosis, central serous chorioretinopathy, multifocal choroiditis, choroidal neovascularization, choroidal thickness, choroidal vascularity index, choroidal vascular density, and choroidal blood supply. The search terms were used either independently or combined with choriocapillaris/choroid. RESULTS: The imaging techniques which are used to qualitatively and quantitatively analyze choriocapillaris are described. The pathological alterations in the choriocapillaris in an array of conditions such as diabetes mellitus, age-related macular degeneration, pachychoroid spectrum of diseases, and inflammatory disorders have been comprehensively reviewed. The future directions in the study of choriocapillaris have also been discussed. CONCLUSION: The development of imaging tools such as OCT and OCTA has dramatically improved the assessment of choriocapillaris in health and disease. The choriocapillaris can be delineated from the stromal choroid using the OCT and quantified by manual or automated methods. However, these techniques have inherent limitations due to the lack of an anatomical distinction between the choriocapillaris and the stromal choroid, which can be overcome with the use of predefined segmentation slabs on OCT and OCTA. These segmentation slabs help in standardizing the choriocapillaris imaging and obtain repeatable measurements in various conditions such as diabetic retinopathy, age-related macular degeneration, pachychoroid spectrum, and ocular inflammations. Additionally, Doppler imaging has also been effectively used to evaluate the choroidal blood flow and quantifying the choriocapillaris and establishing its role in the pathogenesis of various retinochoroidal diseases. As tremendous technological advancements such as wide-field and ultra-wide field imaging take place, there will be a significant improvement in the ease and accuracy of quantifying the choriocapillaris.
Garg I, Uwakwe C, Le R, Lu ES, Cui Y, Wai KM, Katz R, Zhu Y, Moon JY, Li CY, Laíns I, Eliott D, Elze T, Kim LA, Wu DM, Miller JW, Husain D, Vavvas DG, Miller JB. Nonperfusion Area and Other Vascular Metrics by Wider Field Swept-Source OCT Angiography as Biomarkers of Diabetic Retinopathy Severity. Ophthalmol Sci 2022;2(2)Abstract
Purpose: To study the wider field swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, especially non-perfusion area (NPA), in the diagnosing and staging of DR. Design: Cross-sectional observational study (November 2018-September 2020). Participants: 473 eyes of 286 patients (69 eyes of 49 control patients and 404 eyes of 237 diabetic patients). Methods: We imaged using 6mm×6mm and 12mm×12mm angiograms on WF SS-OCTA. Images were analyzed using the ARI Network and FIJI ImageJ. Mixed effects multiple regression models and receiver operator characteristic analysis was used for statistical analyses. Main Outcome Measures: Quantitative metrics such as vessel density (VD); vessel skeletonized density (VSD); foveal avascular zone (FAZ) area, circularity, and perimeter; and NPA in DR and their relative performance for its diagnosis and grading. Results: Among patients with diabetes (median age 59 years), 51 eyes had no DR, 185 eyes (88 mild, 97 moderate-severe) had non-proliferative DR (NPDR); and 168 eyes had proliferative DR (PDR). Trend analysis revealed a progressive decline in superficial capillary plexus (SCP) VD and VSD, and increased NPA with increasing DR severity. Additionally, there was a significant reduction in deep capillary plexus (DCP) VD and VSD in early DR (mild NPDR), but the progressive reduction in advanced DR stages was not significant. NPA was the best parameter to diagnose DR (AUC:0.96), whereas all parameters combined on both angiograms efficiently diagnosed (AUC:0.97) and differentiated between DR stages (AUC range:0.83-0.97). The presence of diabetic macular edema was associated with reduced SCP and DCP VD and VSD within mild NPDR eyes, whereas an increased VD and VSD in SCP among moderate-severe NPDR group. Conclusions: Our work highlights the importance of NPA, which can be more readily and easily measured with WF SS-OCTA compared to fluorescein angiography. It is additionally quick and non-invasive, and hence can be an important adjunct for DR diagnosis and management. In our study, a combination of all OCTA metrics on both 6mm×6mm and 12mm×12mm angiograms had the best diagnostic accuracy for DR and its severity. Further longitudinal studies are needed to assess NPA as a biomarker for progression or regression of DR severity.
Zeng R, Garg I, Bannai D, Kasetty M, Katz R, Park J, Lizano P, Miller JB. Retinal microvasculature and vasoreactivity changes in hypertension using optical coherence tomography-angiography. Graefes Arch Clin Exp Ophthalmol 2022;260(11):3505-3515.Abstract
PURPOSE: To evaluate the retinal vasculature and vasoreactivity of patients with hypertension (HTN) using spectral domain optical coherence tomography angiography (SD-OCTA). METHODS: Patients with and without a diagnosis of HTN were included in this cross-sectional observational study. All eyes were imaged with SD-OCTA using 3 mm × 3 mm and 6 mm × 6 mm centered on both the fovea and optic disk. A second 6 mm × 6 mm scan was taken after a 30 s breath-hold. Vessel density (VD), vessel skeletonized density (VSD), and fractal dimension (FD) were calculated using customized MATLAB scripts. Vessel diameter index (VDI) was obtained by taking the ratio of VD to VSD. Vasoreactivity was measured by subtracting the VD or VSD before and after breath-hold (∆VD, ∆VSD). RESULTS: Twenty-three eyes with HTN (17 patients) and 17 control eyes (15 patients) were included. In the 6 mm × 6 mm angiogram centered on fovea, the superficial capillary plexus (SCP) VD (ß =  - 0.029, p = 0.012), VSD (ß =  - 0.004, p = 0.043) and the choriocapillaris VD (ß =  - 0.021, p = 0.030) were significantly decreased in HTN compared to control eyes. Similarly, FD was decreased in both the SCP (ß =  - 0.012, p = 0.013) and choriocapillaris (ß =  - 0.009, p = 0.030). In the 3 mm × 3 mm angiogram centered on optic disk, SCP VDI (ß =  - 0.364, p = 0.034) was decreased. ∆VD and ∆VSD were both reduced in the DCP (ß =  - 0.034, p = 0.032; ß =  - 0.013, p = 0.043) and ∆VSD was elevated in the choriocapillaris of HTN eyes (ß = 0.004, p = 0.032). CONCLUSIONS: The study used SD-OCTA to show significant differences in the retinal vasculature of hypertensive patients. It was also the first to demonstrate the potential of OCT-A to investigate retinal vascular reactivity in patients with HTN.
Naninck T, Kahlaoui N, Lemaitre J, Maisonnasse P, De Mori A, Pascal Q, Contreras V, Marlin R, Relouzat F, Delache B, Hérate C, Aldon Y, van Gils M, Zabaleta N, Tsong Fang RH, Bosquet N, Sanders RW, Vandenberghe LH, Chapon C, Le Grand R. Computed tomography and [18F]-FDG PET imaging provide additional readouts for COVID-19 pathogenesis and therapies evaluation in non-human primates. iScience 2022;25(4):104101.Abstract
Non-human primates (NHPs) are particularly relevant as preclinical models for SARS-CoV-2 infection and nuclear imaging may represent a valuable tool for monitoring infection in this species. We investigated the benefit of computed X-ray tomography (CT) and [18F]-FDG positron emission tomography (PET) to monitor the early phase of the disease in a large cohort (n = 76) of SARS-CoV-2 infected macaques. Following infection, animals showed mild COVID-19 symptoms including typical lung lesions. CT scores at the acute phase reflect the heterogeneity of lung burden following infection. Moreover, [18F]-FDG PET revealed that FDG uptake was significantly higher in the lungs, nasal cavities, lung-draining lymph nodes, and spleen of NHPs by 5 days postinfection compared to pre-infection levels, indicating early local inflammation. The comparison of CT and PET data from previous COVID-19 treatments or vaccines we tested in NHP, to this large cohort of untreated animals demonstrated the value of in vivo imaging in preclinical trials.

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