Imaging and Diagnostics

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.

PURPOSE: To establish a numerical spectral-domain optical coherence tomography (SD-OCT)-based keratoconus (KC) staging system and compare it with existing KC staging systems. SETTING: Eye Hospital of Wenzhou Medical University, Wenzhou, China. DESIGNS: Retrospective case-control study. METHODS: Scheimpflug tomography, air-puff tonometry, and SD-OCT were performed on 236 normal and 331 KC eyes. All SD-OCT-derived parameters of the corneal epithelium and stroma were evaluated based on their receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity to discriminate between normal and KC eyes. The best performing parameters were subsequently used to create an OCT-based staging system, which was compared with existing tomographic and biomechanical staging systems. RESULTS: 236 eyes from 236 normal patients and 331 eyes from 331 KC patients of different stages were included. The highest ranked AUC ROC SD-OCT parameters, derived from stroma and epithelium, were stroma overall minimum thickness (ST: AUC 0.836, sensitivity 90%, specificity 67%) and epithelium overall SD (EP: AUC 0.835, sensitivity 75%, specificity 78%). A numerical SD-OCT staging system called STEP including 2 parameters-"ST" and "EP"-with 5 stages was proposed. CONCLUSIONS: The new SD-OCT-based KC staging system is the first to take the epithelium with its sublayer stroma information into account, showing a strong agreement to the existing staging systems. This system could be incorporated into daily practice, potentially leading to an overall improvement in KC treatment and follow-up management.

Adaptive optics provides improved resolution in ophthalmic imaging when retinal microstructures need to be identified, counted, and mapped. In general, multiple images are averaged to improve the signal-to-noise ratio or analyzed for temporal dynamics. Image registration by cross-correlation is straightforward for small patches; however, larger images require more sophisticated registration techniques. Strip-based registration has been used successfully for photoreceptor mosaic alignment in small patches; however, if the deformations along strips are not simple displacements, averaging can degrade the final image. We have applied a non-rigid registration technique that improves the quality of processed images for mapping cones over large image patches. In this approach, correction of local deformations compensates for local image stretching, compressing, bending, and twisting due to a number of causes. The main result of this procedure is improved definition of retinal microstructures that can be better identified and segmented. Derived metrics such as cone density, wall-to-lumen ratio, and quantification of structural modification of blood vessel walls have diagnostic value in many retinal diseases, including diabetic retinopathy and age-related macular degeneration, and their improved evaluations may facilitate early diagnostics of retinal diseases.

BACKGROUND: The clinical application of optical coherence tomography angiography (OCTA) has been well documented in literature with its promising potential in dye-less evaluation of various retinal vascular pathologies. Recent advances in OCTA help us gather wider field of view with 12 mm × 12 mm and montage compared to the standard dye-based scans, which has a higher accuracy and sensitivity in detection of peripheral pathologies. The aim of this study is to build a semi-automated algorithm to precisely quantify the non-perfusion areas (NPAs) on widefield swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: All subjects underwent imaging on 100 kHz SS-OCTA device acquiring 12 mm × 12 mm angiograms centered on fovea and optic disc. After a comprehensive literature review, a novel algorithm using FIJI (ImageJ) was designed to calculate the NPAs (mm2) after excluding the threshold and segmentation artifact areas from the total field of view. Segmentation and threshold artifacts were first removed from enface structure images using the spatial variance and mean filter respectively. Vessel enhancement was achieved by using 'Subtract Background' followed by directional filter. The cut off for Huang's fuzzy black and white thresholding was defined from the pixel values based of the foveal avascular zone. Then, the NPAs were calculated using the 'Analyze Particles' command with a minimum size of ~0.15 mm2. Finally, the artifact area was subtracted from to give the corrected NPAs. RESULTS: Our cohort had 44 eyes of 30 control patients and 107 eyes of 73 patients with diabetes mellitus (both median age 55 years, P=0.89). Of 107 eyes, 21 eyes had no evidence of diabetic retinopathy (DR), 50 eyes had non-proliferative DR and 36 eyes had proliferative DR. The median NPA was 0.20 (0.07-0.40) in controls, 0.28 (0.12-0.72) in no DR, 5.54 (3.12-9.10) in non-proliferative DR and 13.38 (8.73-26.32) in proliferative DR eyes. Using mixed effects-multiple linear regression analysis adjusting for age, there was significant progressive increase in NPA with increasing DR severity. CONCLUSIONS: This is one of the first study to use the directional filter for WFSS-OCTA image processing which is known to be superior to other Hessian based multiscale, linear, and non-linear filters especially for vascular analysis. Our method could greatly refine and streamline the calculation of signal void area proportion, while being much quicker and accurate than manual delineation of NPAs and subsequent estimation. This combined with the wide field of view can have a great prognostic and diagnostic clinical impact for future applications in DR and other ischemic retinal pathologies.

PURPOSE: To evaluate the relationship between contrast sensitivity (CS) and widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vascular metrics in diabetic macular edema (DME) was the purpose. METHODS: This prospectively enrolled cross-sectional observational study included 61 eyes of 48 patients that were tested with the quantitative CS function (qCSF) test on the same day as imaging with WF SS-OCTA (PLEX® Elite 9000, Carl Zeiss Meditec) 3 × 3, 6 × 6, and 12 × 12 mm scans. Outcomes included visual acuity (VA) and multiple qCSF metrics. Vascular metrics included vessel density (VD) and vessel skeletonized density (VSD) in the superficial (SCP) and deep capillary plexus (DCP) and whole retina (WR) and foveal avascular zone (FAZ) parameters. Mixed effects multivariable linear regression models controlling for age, lens status, and diabetic retinopathy stage were performed. Standardized beta coefficients were calculated by refitting the standardized data. RESULTS: SS-OCTA metrics had a significant association with CS and VA. The effect size of OCTA metrics was larger on CS compared to VA. For example, the standardized beta coefficients for VSD and CS at 3 cpd (βSCP = 0.76, βDCP = 0.71, βWR = 0.72, p < 0.001) were larger than those for VA (βSCP =  - 0.55, p < 0.001; βDCP =  - 0.43, p = 0.004; βWR =  - 0.50, p < 0.001). On 6 × 6 mm images, AULCSF, CS at 3 cpd, and CS at 6 cpd were significantly associated with VD and VSD in all three slab types (SCP, DCP, and WR), while VA was not. CONCLUSION: Structure-function associations in patients with DME leveraging the qCSF device suggest microvascular changes on WF SS-OCTA are associated with larger changes in contrast sensitivity than VA.

PURPOSE OF REVIEW: To summarize the recent literature on deep learning (DL) model applications in glaucoma detection and surveillance using posterior segment optical coherence tomography (OCT) imaging. RECENT FINDINGS: DL models use OCT derived parameters including retinal nerve fiber layer (RNFL) scans, macular scans, and optic nerve head (ONH) scans, as well as a combination of these parameters, to achieve high diagnostic accuracy in detecting glaucomatous optic neuropathy (GON). Although RNFL segmentation is the most widely used OCT parameter for glaucoma detection by ophthalmologists, newer DL models most commonly use a combination of parameters, which provide a more comprehensive approach. Compared to DL models for diagnosing glaucoma, DL models predicting glaucoma progression are less commonly studied but have also been developed. SUMMARY: DL models offer time-efficient, objective, and potential options in the management of glaucoma. Although artificial intelligence models have already been commercially accepted as diagnostic tools for other ophthalmic diseases, there is no commercially approved DL tool for the diagnosis of glaucoma, most likely in part due to the lack of a universal definition of glaucoma defined by OCT derived parameters alone (see Supplemental Digital Content 1 for video abstract, http://links.lww.com/COOP/A54 ).

PURPOSE OF REVIEW: Optical coherence tomography angiography (OCTA) is a novel, noninvasive imaging technique, which provides depth resolved visualization of microvasculature of the retina and choroid. Although OCTA has been widely used for the evaluation of a number of retinal diseases, its use in the field of neuro-ophthalmology has been less studied. In this review, we provide an update on the utility of OCTA in neuro-ophthalmic conditions. RECENT FINDINGS: Peripapillary and macular microvasculature analyses have indicated that OCTA can be a promising tool for early detection of a number of neuro-ophthalmic diseases, differential diagnosis, and monitoring of disease progression. Recent studies have demonstrated that structural and functional impairment can develop at early stages in some conditions such as in multiple sclerosis and Alzheimer's disease even in the absence of overt clinical symptoms. Furthermore, this dye-less technique can be a valuable adjunct tool in the detection of complications commonly seen in some congenital entities such optic disc drusen. SUMMARY: Since its introduction, OCTA has emerged as an important imaging approach shedding light on unrevealed pathophysiological mechanisms of several ocular diseases. The use of OCTA as a biomarker in the field of neuro-ophthalmology has recently gained considerable attention with studies supporting its role in clinical setting while larger studies are warranted for correlating these findings with traditional diagnostic procedures and clinical features and outcomes.

Purpose: To evaluate the impact on surveillance rates for diabetic retinopathy (DR) by providing nonmydriatic retinal imaging as part of comprehensive diabetes care at no cost to patients or insurers. Methods: A retrospective comparative cohort study was designed. Patients were imaged from April 1, 2016 to March 31, 2017 at a tertiary diabetes-specific academic medical center. Retinal imaging was provided without additional cost beginning October 16, 2016. Images were evaluated for DR and diabetic macular edema using standard protocol at a centralized reading center. Diabetes surveillance rates before and after no-cost imaging were compared. Results: A total of 759 and 2,080 patients respectively were imaged before and after offering no-cost retinal imaging. The difference represents a 274% increase in the number of patients screened. Furthermore, there was a 292% and 261% increase in the number of eyes with mild DR and referable DR, respectively. In the comparative 6-month period, 92 additional cases of proliferative DR were identified, estimated to prevent 6.7 cases of severe visual loss with annual cost savings of $180,230 (estimated yearly cost of severe vision loss per person: $26,900). In patients with referable DR, self-awareness was low, with no significant difference in the before and after groups (39.4% vs. 43.8%, p = 0.3725). Conclusions: Providing retinal imaging as part of comprehensive diabetes care substantially increased the number of patients identified by nearly threefold. The data suggest that the removal of out-of-pocket costs substantially increased patient surveillance rates, which may translate to improved long-term patient outcomes.

BACKGROUND: Previous studies have indicated that pain-related diseases can result in significant functional alterations in the brain. However, differences in spontaneous brain activity in toothache (TA) patients remain unclear. OBJECTIVE: To investigate altered spontaneous brain activity in patients with TA and its underlying mechanisms using the resting-state functional magnetic resonance imaging-fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF) technique. METHODS: Twelve patients with TA and 12 non-toothache controls (NTCs) (matched for sex, age, and level of education) were enrolled. Spontaneous cerebral activity variations were investigated using the rsfMRI-fALFF technique in all individuals. The mean fALFF values of the TA patients and NTCs were classified using receiver operating characteristic (ROC) curves. The correlations between fALFF signals of distinct brain regions and clinical manifestations of TA patients were evaluated using Pearson's correlation analysis. RESULTS: TA patients showed lower fALFF values in the left superior frontal gyrus, medial; right superior frontal gyrus, dorsolateral; and left median cingulate and paracingulate gyri (LDCG) than the NTCs. Moreover, ROC curve analysis indicated that the area under the curve of each cerebral region studied had high accuracy. Besides, in the TA group, the visual analog scale score was negatively correlated with fALFF signal values of the LDCG (r = .962, p < .001). CONCLUSION: Abnormal spontaneous activity was detected in numerous brain regions in patients with TA, which may be valuable for understanding the brain processing mechanism underlying TA. These regional changes in brain activity may serve as effective clinical indicators of TA.

PURPOSE: To evaluate the potential of retinal optical coherence tomography (OCT) measurements and polygenic risk scores (PRS) to identify people at risk of cognitive impairment. METHODS: Using OCT images from 50 342 UK Biobank participants, we examined associations between retinal layer thickness and genetic risk for neurodegenerative disease and combined these metrics with PRS to predict baseline cognitive function and future cognitive deterioration. Multivariate Cox proportional hazard models were used to predict cognitive performance. P values for retinal thickness analyses are false-discovery-rate-adjusted. RESULTS: Higher Alzheimer's disease PRS was associated with a thicker inner nuclear layer (INL), chorio-scleral interface (CSI) and inner plexiform layer (IPL) (all p<0.05). Higher Parkinson's disease PRS was associated with thinner outer plexiform layer (p<0.001). Worse baseline cognitive performance was associated with thinner retinal nerve fibre layer (RNFL) (aOR=1.038, 95% CI (1.029 to 1.047), p<0.001) and photoreceptor (PR) segment (aOR=1.035, 95% CI (1.019 to 1.051), p<0.001), ganglion cell complex (aOR=1.007, 95% CI (1.002 to 1.013), p=0.004) and thicker ganglion cell layer (aOR=0.981, 95% CI (0.967 to 0.995), p=0.009), IPL (aOR=0.976, 95% CI (0.961 to 0.992), p=0.003), INL (aOR=0.923, 95% CI (0.905 to 0.941), p<0.001) and CSI (aOR=0.998, 95% CI (0.997 to 0.999), p<0.001). Worse future cognitive performance was associated with thicker IPL (aOR=0.945, 95% CI (0.915 to 0.999), p=0.045) and CSI (aOR=0.996, 95% CI (0.993 to 0.999) 95% CI, p=0.014). Prediction of cognitive decline was significantly improved with the addition of PRS and retinal measurements. CONCLUSIONS AND RELEVANCE: Retinal OCT measurements are significantly associated with genetic risk of neurodegenerative disease and may serve as biomarkers predictive of future cognitive impairment.

PURPOSE: To evaluate the ability of ultrawide field (UWF)-directed optical coherence tomography (OCT) to detect retinal neovascularization in eyes thought to have severe nonproliferative diabetic retinopathy (NPDR). METHODS: Retrospective study of 20 consecutive patients diagnosed with severe NPDR by clinical examination. All patients underwent UWF color imaging (UWF-CI) and UWF-directed OCT following a prespecified imaging protocol to assess the mid periphery, 15/32 (46.9%) eyes underwent UWF-fluorescein angiography (FA). On OCT, new vessels elsewhere (NVE) were defined when vessels breached the internal limiting membrane. RESULTS: A total of 32 eyes of 20 patients were evaluated. Of the 45 suspected areas of intraretinal microvascular abnormalities (IRMA) on UWF-CI, 38 (84.4%) were imaged by UWF-directed OCT, and 9/38 IRMA (23.7%) were NVE by OCT. Furthermore, UWF-directed OCT identified seven additional NVE in three eyes not seen on UWF-CI. This resulted in a change in diabetic retinopathy (DR) severity from severe NPDR to PDR in 8/32 eyes (25.0%). Among the 46.9% of eyes with UWF-FA, UWF-directed OCT agreed with the UWF-FA findings in 80% (12/15 eyes), missing only one peripheral NVE outside the UWF-OCT scanning area. Two eyes had subtle NVD that were not evident on UWF-directed OCT. CONCLUSIONS: This pilot study suggests that UWF-directed OCT may help differentiate IRMA from NVE and detect unrecognized NVE in eyes with advanced DR in a clinical practice setting. Future prospective studies in larger cohorts could determine whether this rapid and noninvasive method is clinically relevant in determining NVE presence or retinopathy progression and complication risk. TRANSLATIONAL RELEVANCE: UWF-directed OCT may offer a noninvasive alternative to detect NVE in eyes with DR.

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.

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.

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.

PURPOSE: We compare the ability of resident physicians to identify retinal breaks on ultra-widefield color fundus photos using the traditional image compared to an image with a green filter overlay. METHODS: Residents were shown fundus photos of 10 eyes with either a retinal tear or hole. Participants were shown each photo twice-once with traditional color settings and once with a green filter overlay. Participants were scored on whether the break was correctly identified and timed on how long it took to identify the pathology. RESULTS: Residents were able to correctly identify more retinal breaks on fundus photos with a green filter overlay compared to photos with traditional settings (P = 0.02). Residents were also able to identify breaks on fundus photos more quickly on images with a green filter overlay compared to the traditional images (P < 0.001). CONCLUSIONS: The application of a green filter overlay may help in identifying retinal breaks.