Imaging and Diagnostics

Guzman Aparicio MA, Chen TC. New views on three-dimensional imaging technologies for glaucoma: an overview. Curr Opin Ophthalmol 2022;33(2):103-111.Abstract
PURPOSE OF REVIEW: To summarize the literature on three-dimensional (3D) technological advances in ophthalmology, the quantitative methods associated with this, and their improved ability to help detect glaucoma disease progression. RECENT FINDINGS: Improvements in measuring glaucomatous structural changes are the result of dual innovations in optical coherence tomography (OCT) imaging technology and in associated quantitative software. SUMMARY: Compared with two-dimensional (2D) OCT parameters, newer 3D parameters provide more data and fewer artifacts.
Bannai D, Adhan I, Katz R, Kim LA, Keshavan M, Miller JB, Lizano P. Quantifying Retinal Microvascular Morphology in Schizophrenia Using Swept-Source Optical Coherence Tomography Angiography. Schizophr Bull 2022;48(1):80-89.Abstract
BACKGROUND: Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ. METHODS: This study included 30 patients with SZ/schizoaffective disorder (8 early and 15 chronic) and 22 healthy controls (HCs). All assessments were performed at Beth Israel Deaconess Medical Center and Massachusetts Eye and Ear. All participants underwent swept-source OCT-A of right (oculus dextrus [OD]) and left (oculus sinister [OS]) eye, clinical, and cognitive assessments. Macular OCT-A images (6 × 6 mm) were collected with the DRI Topcon Triton for superficial, deep, and choriocapillaris vascular regions. Microvasculature was quantified using vessel density (VD), skeletonized vessel density (SVD), fractal dimension (FD), and vessel diameter index (VDI). RESULTS: Twenty-one HCs and 26 SZ subjects were included. Compared to HCs, SZ patients demonstrated higher overall OD superficial SVD, OD choriocapillaris VD, and OD choriocapillaris SVD, which were primarily observed in the central, central and outer superior, and central and outer inferior/superior, respectively. Early-course SZ subjects had significantly higher OD superficial VD, OD choriocapillaris SVD, and OD choriocapillaris FD compared to matched HCs. Higher bilateral (OU) superficial VD correlated with lower Positive and Negative Syndrome Scale (PANSS) positive scores, and higher OU deep VDI was associated with higher PANSS negative scores. CONCLUSIONS AND RELEVANCE: These results suggest the presence of microvascular dysfunction associated with early-stage SZ. Clinical associations with microvascular alterations further implicate this hypothesis, with higher measures being associated with worse symptom severity and functioning in early stages and with lower symptom severity and better functioning in later stages.
Wang JC, Lu Y, Sobrin L, Husain D. MULTIMODAL IMAGING IN ACUTE RETINAL NECROSIS PRESENTING WITH MACULAR INVOLVEMENT. Retin Cases Brief Rep 2022;16(3):347-350.Abstract
PURPOSE: To report an unusual case of early macular necrosis in acute retinal necrosis and its features on multimodal imaging. METHODS: Findings on fundus examination, laboratory workup, fluorescein angiography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography. RESULTS: A 31-year-old healthy woman presented with 1 week of photophobia and central scotoma of the right eye. Initial examination revealed vitritis, hyperemia of the optic disc, and a yellow-white macular lesion without any peripheral findings. Peripheral involvement was first noted only 4 days later. The patient was diagnosed with acute retinal necrosis secondary to varicella zoster virus and was successfully treated with intravitreal and oral antiviral medications. Optical coherence tomography imaging of the macular lesion showed involvement of both the inner and outer retina. Optical coherence tomography angiography revealed a large flow void in the choriocapillaris, which has not been previously demonstrated. CONCLUSION: Multimodal imaging offers valuable information in the evaluation of patients with acute retinal necrosis.
Inomata T, Nakamura M, Sung J, Midorikawa-Inomata A, Iwagami M, Fujio K, Akasaki Y, Okumura Y, Fujimoto K, Eguchi A, Miura M, Nagino K, Shokirova H, Zhu J, Kuwahara M, Hirosawa K, Dana R, Murakami A. Smartphone-based digital phenotyping for dry eye toward P4 medicine: a crowdsourced cross-sectional study. NPJ Digit Med 2021;4(1):171.Abstract
Multidimensional integrative data analysis of digital phenotyping is crucial for elucidating the pathologies of multifactorial and heterogeneous diseases, such as the dry eye (DE). This crowdsourced cross-sectional study explored a novel smartphone-based digital phenotyping strategy to stratify and visualize the heterogenous DE symptoms into distinct subgroups. Multidimensional integrative data were collected from 3,593 participants between November 2016 and September 2019. Dimension reduction via Uniform Manifold Approximation and Projection stratified the collected data into seven clusters of symptomatic DE. Symptom profiles and risk factors in each cluster were identified by hierarchical heatmaps and multivariate logistic regressions. Stratified DE subgroups were visualized by chord diagrams, co-occurrence networks, and Circos plot analyses to improve interpretability. Maximum blink interval was reduced in clusters 1, 2, and 5 compared to non-symptomatic DE. Clusters 1 and 5 had severe DE symptoms. A data-driven multidimensional analysis with digital phenotyping may establish predictive, preventive, personalized, and participatory medicine.
Sun JK, Josic K, Melia M, Glassman AR, Bailey C, Chalam KV, Chew EY, Cukras C, Grover S, Jaffe GJ, Lee R, Nielsen JS, Thompson DJS, Wiley HE, Ferris FL, Ferris FL. Conversion of Central Subfield Thickness Measurements of Diabetic Macular Edema Across Cirrus and Spectralis Optical Coherence Tomography Instruments. Transl Vis Sci Technol 2021;10(14):34.Abstract
Purpose: Develop equations to convert Cirrus central subfield thickness (CST) to Spectralis CST equivalents and vice versa in eyes with diabetic macular edema (DME). Methods: The DRCR Retina Network Protocol O data were split randomly to train (70% sample) and validate (30% sample) conversion equations. Data from an independent study (CADME) also validated the equations. Bland-Altman 95% limits of agreement between predicted and observed values evaluated the equations. Results: Protocol O included 374 CST scan pairs from 187 eyes (107 participants). The CADME study included 150 scan pairs of 37 eyes (37 participants). Proposed conversion equations are Spectralis = 40.78 + 0.95 × Cirrus and Cirrus = 1.82 + 0.94 × Spectralis regardless of age, sex, or CST. Predicted values were within 10% of observed values in 101 (90%) of Spectralis and 99 (88%) of Cirrus scans in the validation data; and in 136 (91%) of the Spectralis and 148 (99%) of the Cirrus scans in the CADME data. Adjusting for within-eye correlations, 95% of conversions are estimated to be within 17% (95% confidence interval, 14%-21%) of CST on Spectralis and within 22% (95% confidence interval, 18%-28%) of CST on Cirrus. Conclusions: Conversion equations developed in this study allow the harmonization of CST measurements for eyes with DME using a mix of current Cirrus and Spectralis device images. Translational Relevance: The CSTs measured on Cirrus and Spectralis devices are not directly comparable owing to outer boundary segmentation differences. Converting CST values across spectral domain optical coherence tomography instruments should benefit both clinical research and standard care efforts.
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;99(7):e1198-e1205.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.
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;46(12):1777-1791.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.
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.
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.
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.

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