Correction: Díaz-Aljaro et al. Quantitative Microvascular Change Analysis Using a Semi-Automated Algorithm in Macula-on Rhegmatogenous Retinal Detachment Assessed by Swept-Source Optical Coherence Tomography Angiography. Diagnostics 2024, 14, 750.

In the original publication [...].

Quantitative Microvascular Change Analysis Using a Semi-Automated Software in Macula-off Rhegmatogenous Retinal Detachment Assessed by Swept-Source Optical Coherence Tomography Angiography.

Objective: To analyze the performance of custom semi-automated software for quantitative analysis of retinal capillaries in eyes with macula-off rhegmatogenous retinal detachment (RRD) and the role of these microvascular measures as potential biomarkers of postoperative visual outcomes. Methods: A prospective, observational, and single-center study was conducted on consecutive patients who underwent 25G pars-plana vitrectomy for primary uncomplicated macula-off RRD. Optical coherence tomography angiography (OCTA) was performed in the fellow and RRD eyes before surgery and in months 1, 3, and 6 after surgery. The preoperative values of the fellow eyes were used as surrogates of macula-off ones. The primary endpoints were the mean vessel diameter index (VDI); vessel area density (VAD); and vessel skeleton density (VSD) at month 6. Results: Forty-four eyes (44 patients) were included in the study. Considering the fellow eyes as a surrogate of preoperative values of macula-off eyes, VDI in superficial (SCP) and deep (DCP) capillary plexuses was significantly reduced at month 6 (p = 0.0087 and p = 0.0402, respectively); whereas VSD in SCP increased significantly from preoperative values (p = 0.0278). OCTA built-in software parameters were significantly reduced from month 1 to month 6 in both SCP and DCP (p values ranged between 0.0235 and <0.0001). At month 6, 25 (56.8%) eyes achieved a best-corrected visual acuity BCVA ≥ 0.3 (LogMAR). The greater the preoperative BCVA, the greater the probability of achieving good visual outcomes (Odds ratio: 11.06; p = 0.0037). However, none of the OCTA parameters were associated with the probability of achieving a BCVA improvement ≥ 0.3. Conclusions: Quantitative evaluation of capillary density and morphology through OCTA and semi-automated software represents a valuable tool for clinical assessment and managing the disease comprehensively.

Quantitative Microvascular Change Analysis Using a Semi-Automated Algorithm in Macula-on Rhegmatogenous Retinal Detachment Assessed by Swept-Source Optical Coherence Tomography Angiography.

PURPOSE: The purpose of this study was to objectively evaluate the longitudinal changes observed in the retinal capillaries in eyes with macula-on rhegmatogenous retinal detachment (RRD), assessed with optical coherence tomography angiography (OCTA), and to assess the role of these microvascular measures as potential biomarkers of postoperative visual outcomes. METHODS: This was a prospective, longitudinal study conducted on consecutive patients who underwent 25 G pars plana vitrectomy for primary RRD. The vessel area density (VAD), vessel skeleton density (VSD), and vessel diameter index (VDI) were assessed in the superficial (SCP) and deep (DCP) capillary plexuses. RESULTS: Twenty-three eyes with macula-on RRD were included in the study. The mean preoperative VDI, VAD, and VSD of the RRD eye were 18.6 ± 1.1, 0.43 ± 0.02, and 0.17 ± 0.01 in the SCP; and 18.6 ± 0.6, 0.38 ± 0.03, and 0.15 ± 0.01 in the DCP, respectively. At month 6, eight (34.8%) eyes achieved a best-corrected visual acuity (BCVA) gain ≥ 0.1 LogMAR. A preoperative VDI > 17.80, VSD > 0.170, and VDI-change > -0.395 in the SCP; and VDI > 18.11 and VDI change > -0.039 in the DCP were predictors of achieving a BCVA-gain ≥ 0.1 LogMAR. CONCLUSIONS: The preoperative VDI in SCP and DCP, the preoperative VSD in SCP, and their changes from preoperative values were predictors of visual outcomes. A quantitative OCTA analysis of capillary density and morphology may represent a potential predictive tool for surgical outcomes in RRD. The results reported in this study suggest that OCTA is a useful ancillary test for clinical disease management.

Feasibility of cross-vendor linkage of ophthalmic images with electronic health record data: an analysis from the IRIS Registry®.

Purpose: To link compliant, universal Digital Imaging and Communications in Medicine (DICOM) ophthalmic imaging data at the individual patient level with the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight). Design: A retrospective study using de-identified EHR registry data. Subjects Participants Controls: IRIS Registry records. Materials and Methods: DICOM files of several imaging modalities were acquired from two large retina ophthalmology practices. Metadata tags were extracted and harmonized to facilitate linkage to the IRIS Registry using a proprietary, heuristic patient-matching algorithm, adhering to HITRUST guidelines. Linked patients and images were assessed by image type and clinical diagnosis. Reasons for failed linkage were assessed by examining patients' records. Main Outcome Measures: Success rate of linking clinicoimaging and EHR data at the patient level. Results: A total of 2 287 839 DICOM files from 54 896 unique patients were available. Of these, 1 937 864 images from 46 196 unique patients were successfully linked to existing patients in the registry. After removing records with abnormal patient names and invalid birthdates, the success linkage rate was 93.3% for images. 88.2% of all patients at the participating practices were linked to at least one image. Conclusions and Relevance: Using identifiers from DICOM metadata, we created an automated pipeline to connect longitudinal real-world clinical data comprehensively and accurately to various imaging modalities from multiple manufacturers at the patient and visit levels. The process has produced an enriched and multimodal IRIS Registry, bridging the gap between basic research and clinical care by enabling future applications in artificial intelligence algorithmic development requiring large linked clinicoimaging datasets.

Decreased Central Macular Choriocapillaris Perfusion Correlates With Increased Low Luminance Visual Acuity Deficits.

PURPOSE: Correlations between low luminance visual acuity deficits (LLVADs) and central choriocapillaris perfusion deficits were investigated to help explain how increases in LLVAD scores at baseline predict annual growth rates of geographic atrophy (GA). DESIGN: Prospective cross-sectional study. METHODS: Photopic luminance best-corrected visual acuity (PL-BCVA) and low luminance BCVA (LL-BCVA) were measured using the Early Treatment Diabetic Retinopathy Study chart. LL-BCVA was measured using a 2.0-log unit neutral density filter. LLVADs were calculated as the difference between PL-BCVA and LL-BCVA. Within a fovea-centered 1-mm circle, the percentage of choriocapillaris flow deficits (CC FD%), drusen volume, optical attenuation coefficient (OAC) elevation volume, and outer retinal layer (ORL) thickness were assessed. RESULTS: In all 90 eyes (30 normal eyes; 31 drusen-only eyes; 29 non-foveal GA eyes), significant correlations were found between the central CC FD% and PL-BCVA (r = -0.393, P < .001), LL-BCVA (r = -0.534, P < .001), and the LLVAD (r = 0.439, P < .001). Central cube root (cubrt) drusen volume, cubrt OAC elevation volume, and ORL thickness were correlated with PL-BCVA, LL-BCVA, and LLVADs (all P < .05). Stepwise regression models showed that central cubrt OAC elevation volume and ORL thickness were associated with PL-BCVA (R2 = 0.24, P < .05); central CC FD%, cubrt OAC elevation volume, and ORL thickness were associated with LL-BCVA (R2 = 0.44, P < .01); and central CC FD% and ORL thickness were associated with LLVAD (R2 = 0.24, P < .01). CONCLUSIONS: The significant correlations between central CC FD% and LLVAD support the hypothesis that the ability of LLVAD to predict the growth of GA is mediated through a decrease in macular choriocapillaris perfusion.

Variability of Vascular Reactivity in the Retina and Choriocapillaris to Oxygen and Carbon Dioxide Using Optical Coherence Tomography Angiography.

Purpose: To investigate the regional and layer-specific vascular reactivity of the healthy human retina and choriocapillaris to changes in systemic carbon dioxide or oxygen. Methods: High-resolution 3 × 3-mm2 optical coherence tomography angiography (OCTA) images were acquired from the central macula, temporal macula, and peripapillary retina while participants were exposed to three gas breathing conditions-room air, 5%CO2, and 100% O2. OCTA from all three regions were extracted and the apparent skeletonized vessel density (VSD) was assessed. The mean flow deficit sizes (MFDSs) of the choriocapillaris were also assessed. Repeated-measures analysis of variance was used to compare the ratio of intrasubject VSD change induced by the gas conditions from baseline in the superficial retinal layer (SRL) and deep retinal layer (DRL) for each retinal region independently, as well as the MFDS of the choriocapillaris. We also compared the vessel reactivity between the retinal capillaries and the choriocapillaris. Results: The cumulative intrasubject response to the gas conditions differed significantly among regions of the SRL (F(2, 7) = 28.22, P < 0.001), with the temporal macula showing the largest response (15%) compared to the macula (8%) and radial peripapillary capillaries (7%). A similar trend was found in the DRL. The choriocapillaris reactivity was similar between the macula (5.8%) and temporal macula (5.6%). There was also a significant heterogeneity in the layer-specific gas responses, with the DRL showing the largest response (28.2%) and the choriocapillaris showing the smallest response (2.8%). Conclusions: Capillary reactivity to changes in inhaled O2 and CO2 is spatially heterogeneous across the retina but not choriocapillaris.

A Deep Learning Model for Automated Segmentation of Geographic Atrophy Imaged Using Swept-Source OCT.

PURPOSE: To present a deep learning algorithm for segmentation of geographic atrophy (GA) using en face swept-source OCT (SS-OCT) images that is accurate and reproducible for the assessment of GA growth over time. DESIGN: Retrospective review of images obtained as part of a prospective natural history study. SUBJECTS: Patients with GA (n = 90), patients with early or intermediate age-related macular degeneration (n = 32), and healthy controls (n = 16). METHODS: An automated algorithm using scan volume data to generate 3 image inputs characterizing the main OCT features of GA-hypertransmission in subretinal pigment epithelium (sub-RPE) slab, regions of RPE loss, and loss of retinal thickness-was trained using 126 images (93 with GA and 33 without GA, from the same number of eyes) using a fivefold cross-validation method and data augmentation techniques. It was tested in an independent set of one hundred eighty 6 × 6-mm2 macular SS-OCT scans consisting of 3 repeated scans of 30 eyes with GA at baseline and follow-up as well as 45 images obtained from 42 eyes without GA. MAIN OUTCOME MEASURES: The GA area, enlargement rate of GA area, square root of GA area, and square root of the enlargement rate of GA area measurements were calculated using the automated algorithm and compared with ground truth calculations performed by 2 manual graders. The repeatability of these measurements was determined using intraclass coefficients (ICCs). RESULTS: There were no significant differences in the GA areas, enlargement rates of GA area, square roots of GA area, and square roots of the enlargement rates of GA area between the graders and the automated algorithm. The algorithm showed high repeatability, with ICCs of 0.99 and 0.94 for the GA area measurements and the enlargement rates of GA area, respectively. The repeatability limit for the GA area measurements made by grader 1, grader 2, and the automated algorithm was 0.28, 0.33, and 0.92 mm2, respectively. CONCLUSIONS: When compared with manual methods, this proposed deep learning-based automated algorithm for GA segmentation using en face SS-OCT images was able to accurately delineate GA and produce reproducible measurements of the enlargement rates of GA.

Ocular and systemic determinants of perifoveal and macular vessel parameters in healthy African Americans.

PURPOSE: To determine the relationship of various systemic and ocular characteristics with perifoveal and macular vessel density in healthy African American eyes. DESIGN: A population-based cross-sectional study of prospectively recruited African Americans ≥40 years of age. Participants underwent 3×3 mm and 6×6 mm macula scans using spectral-domain optical coherence tomography angiography (OCTA), clinical examinations and clinical questionnaires. Participants with glaucoma, severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and macular oedema were excluded. Custom MATLAB based software quantified vessel area density (VAD) and vessel skeleton density (VSD) in the superficial retinal layer of the macula. Multivariable regression analysis, controlling for inter-eye correlation, was performed to determine systemic and ocular determinants of macular vessel metrics using stepwise selection. Candidate variables included: age, gender, body mass index, history of smoking, history of diabetes, diabetes duration, history of stroke or brain haemorrhage, systolic blood pressure, diastolic blood pressure (DBP), pulse pressure, mean arterial pressure, central subfield thickness (CSFT), visual field mean deviation, intraocular pressure, axial length (AL), mean ocular perfusion pressure and signal strength (SS). RESULTS: A total of 2221 OCTA imaged eyes from 1472 participants were included in this study. Reduced perifoveal and macular VAD and VSD were independently associated with longer AL, reduced SS, reduced CSFT and older age. Male gender and lower DBP were also associated with reduced perifoveal and macular VSD. CONCLUSIONS: When interpreting OCTA images in a clinical setting, it is important to consider the effects ocular and systemic characteristics may have on the macular microcirculation.

A moderate dosage of coffee causes acute retinal capillary perfusion decrease in healthy young individuals.

AIM: Caffeinated beverages are very popular across populations and cultures, but quantitative evidence of the acute effects of moderate coffee doses on retinal perfusion is sparse and contradicting. Thus, the aim of this randomized, cross-over and parallel-group design study was to investigate whether moderate consumption of coffee alters macular retinal capillary perfusion in young healthy individuals. METHODS: Twenty-seven young healthy individuals were recruited for this study. Acute changes in retinal microvasculature were assessed using spectral-domain optical coherence tomography angiography (SD-OCTA) at baseline, 0.5 h, and 2 h after intake of coffee, or water. Meanwhile, cerebral blood flow (CBF) and retina-choroid blood flow were evaluated in a parallel-group design (4 participants each in coffee or water group) using magnetic resonance imaging (MRI) with pseudo-continuous arterial spin labeling sequences. RESULTS: Two hours after coffee intake, blood caffeine concentration increased from 0 to 5.05 ± 1.36 µg/mL. Coffee caused a significant decrease in retinal vessel diameter index (VDI) (19.05 ± 0.24 versus [vs] 19.13 ± 0.26; p < 0.001) and CBF in the frontal lobe (77.47 ± 15.21 mL/100 mL/min vs. 84.13 ± 15.55 mL/100 mL/min; p < 0.05) 2 h after intake. However, it significantly increased retina-choroid blood flow after 0.5 and 2 h (163.18 ± 61.07 mL/100 mL/min vs. 132.68 ± 70.47 mL/100 mL/min, p < 0.001, and 161.21 ± 47.95 vs. 132.68 ± 70.47; p < 0.001, respectively). CONCLUSION: This is the first study to demonstrate the acute effects of daily dose coffee consumption on retinal capillary perfusion using SD-OCTA combinate with blood flow MRI. The findings imply that although moderate coffee intake caused a significant increase in retina-choroid blood flow, there was a significant acute decrease both in macular retinal capillary perfusion and CBF.

Impact of Reticular Pseudodrusen on Choriocapillaris Flow Deficits and Choroidal Structure on Optical Coherence Tomography Angiography.

Purpose: To examine the impact of reticular pseudodrusen (RPD) on choriocapillaris blood flow and choroidal structure in individuals with intermediate age-related macular degeneration (AMD). Methods: Individuals with bilateral large drusen underwent optical coherence tomography (OCT), color fundus photography, near-infrared reflectance, and fundus autofluorescence imaging to determine the presence of RPD. These participants also underwent swept-source OCT angiography (SS-OCTA) imaging to determine (1) choriocapillaris flow deficit (FD) parameters, including the percentage, mean size, and number of FDs present; and (2) choroidal structural parameters, including mean choroidal thickness and choroidal vascularity index. Differences in these parameters between eyes with and without coexistent RPD were examined with and without adjustment for potential key confounders such as drusen volume from the SS-OCTA scans and age. Results: This study included 102 eyes from 51 individuals with bilateral large drusen, and the analyses showed that there were no significant differences in the choriocapillaris FD parameters (P ≥ 0.062 for all) and choroidal structural parameters (P ≥ 0.059 for all), with or without adjustment for potential confounders in this cohort. However, the percentage of FDs and the mean FD size were both significantly greater with increasing drusen volume (P ≤ 0.038 for both). Conclusions: The coexistence of RPD in eyes of individuals with intermediate AMD was not associated with significant impairments in choriocapillaris blood flow and choroidal vascular structural changes, with or without adjustment for key confounders. These findings suggest that macular changes in these vascular parameters may not be associated with the presence of RPD.

Early Retinal Microvasculopathy in Prediabetic Patients and Correlated Factors.

INTRODUCTION: We aimed to detect early retinal microcirculation changes in prediabetic patients and investigate their correlation with clinical examinations. METHODS: Forty-seven prediabetic individuals, 29 controls, and 81 type 2 diabetic mellitus (T2DM) patients were enrolled in this study. A review of clinical data and spectral-domain optical coherence tomography angiography (SD-OCTA) parameters of macular vessel diameter (VD), foveal avascular zone (FAZ), and macular vessel area density (VAD) was performed. RESULTS: Levels of low-density lipoprotein cholesterol and triglycerides in prediabetes and T2DM groups were significantly higher than those in the control group. Urine microalbumin-to-creatinine ratio (ACR) was mildly and moderately increased in the prediabetes and T2DM groups, respectively. Estimated glomerular filtration rate of the three groups were within the normal range. SD-OCTA showed that VAD in the superficial macular area was decreased in the prediabetes group compared to the control group (p=0.01). The FAZ size, particularly in the deep layer, was expanded in the prediabetes group. In the deep retinal layer of the macular area, VD and FAZ size in the prediabetes group were larger than those in the control group. In the prediabetes group, the axial length was significantly correlated with macular VD and FAZ size (p<0.05), and ACR was correlated with FAZ size (p<0.05). Age had a negative correlation with VAD (p<0.01). ACR had a positive correlation with FAZ size (p<0.05). CONCLUSIONS: Enlargement and irregularity of the FAZ area, deep capillary dilation, and decrease in VAD occur in the retina of prediabetes patients with mild kidney function impairment.

CHANGE IN CHORIOCAPILLARIS FLOW DEFICITS WITHIN TEARS OF THE RETINAL PIGMENT EPITHELIUM IMAGED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: Choriocapillaris (CC) flow deficits (FDs) were measured in the areas exposed by tears of the retinal pigment epithelium (RPE) before and after their onset to determine their change over time. METHODS: Patients enrolled in a prospective, swept-source optical coherence tomography angiography (SS-OCTA) study were retrospectively reviewed for RPE tears, and scans were evaluated before and after RPE tear formation. Choriocapillaris flow deficits were measured within the bed of the tear and within a symmetric control region. RESULTS: Three patients with RPE tears were imaged before tear formation and for at least 16 months afterward. When the baseline and first posttear visit were compared, CC FDs decreased by 1.0% in the tear region and 1.7% in the control region ( P = 0.84). When the 16-month follow-up visits were compared with the first post-RPE tear visits, CC FDs decreased by 1.9% in tear regions and increased by 1.3% in control regions ( P = 0.37). CONCLUSION: No significant changes in CC FDs were observed before and after RPE tear formation and for 16 months afterward, suggesting that CC FDs can be reliably detected in the presence of an intact RPE and the absence of the RPE did not affect CC perfusion for at least 16 months.

Repeatability and Reproducibility of 4.5 by 4.5 mm Peripapillary Optical Coherence Tomography Angiography Scans in Glaucoma and Non-Glaucoma Eyes.

PRCIS: Peripapillary vessel parameters from optical coherence tomography angiography (OCTA) 4.5×4.5 mm scans in nonglaucomatous and glaucomatous eyes showed high repeatability and reproducibility, with higher reliability for commercially developed OCTA parameters compared with custom OCTA parameters. PURPOSE: The purpose of this study was to assess intrasession repeatability versus intersession reproducibility of peripapillary vessel parameters from 4.5×4.5 mm OCTA scans in nonglaucomatous eyes and glaucomatous eyes. MATERIALS AND METHODS: In a longitudinal study, peripapillary OCTA scans were quantified using research-oriented custom quantification software that calculated vessel area density (VAD) and flux and clinic-oriented commercially developed software (Cirrus 11.0) that calculated perfusion density (PD) and flux index (FI). Intrasession repeatability and intersession reproducibility were evaluated using within-eye coefficient of variation (CV W ) and intraclass correlation coefficient (ICC). RESULTS: With 127 nonglaucomatous eyes, intrasession CV W for VAD, PD, flux, and FI were 1.900%, 1.174%, 2.787%, and 1.425%, respectively. The intersession CV W were 2.039%, 1.606%, 4.053%, and 2.798%, respectively. Intrasession ICC ranged from 0.903 to 0.956, and intersession ICC ranged from 0.850 to 0.896. Among 144 glaucomatous eyes, intrasession CV W for VAD, PD, flux, and FI were: 3.841%, 1.493%, 5.009%, and 2.432%, respectively. The intersession CV W were 4.991%, 2.155%, 6.360%, and 3.458%, respectively. Intrasession ICC ranged from 0.956 to 0.969, and intersession ICC ranged from 0.918 to 0.964. CONCLUSIONS: Among nonglaucomatous and glaucomatous eyes, the majority of peripapillary OCTA vessel parameters from 4.5×4.5 mm scans had greater intrasession repeatability than intersession reproducibility. There was a greater agreement for the commercially developed quantification parameters than for their custom quantification counterparts.

Intrasession Repeatability and Intersession Reproducibility of Macular Vessel Parameters on Optical Coherence Tomography Angiography in Glaucomatous and Non-Glaucomatous Eyes.

PURPOSE: Using optical coherence tomography angiography (OCTA), this study compared intrasession repeatability versus intersession reproducibility of macular vessel parameters in glaucoma and non-glaucoma subjects. METHODS: 6 × 6 mm2 macular OCTA scans (Cirrus HD-OCT 5000) were acquired from glaucomatous and non-glaucomatous subjects as part of an observational, longitudinal study. Vessel area density (VAD) and vessel skeleton density (VSD) were calculated using research-based quantification software while perfusion density (PDZ) and vessel density (VDZ) were calculated using commercially developed software (Cirrus 11.0, Carl Zeiss Meditec). Intrasession repeatability and intersession reproducibility were determined using within-eye standard deviation (SW), within-eye coefficient of repeatability (CRW), within-eye coefficient of variation (CVW), and intraclass correlation coefficients (ICC). RESULTS: The intrasession repeatability and intersession reproducibility for macular OCTA parameters were similar to one another for both non-glaucomatous and glaucomatous eyes. Intrasession CVW from the non-glaucoma group (n = 73) was 1.097% for VAD, 1.007% for VSD, 2.980% for PDZ, and 2.714% for VDZ. Intersession CVW from the non-glaucoma group (n = 55) was 1.389% for VAD, 1.279% for VSD, 2.935% for PDZ, and 2.695% for VDZ. Intrasession CVW from the glaucoma group (n = 59) was 1.189% for VAD, 0.970% for VSD, 3.827% for PDZ, and 3.542% for VDZ. Intersession CVW from the glaucoma group (n = 45) was 1.412% for VAD, 1.132% for VSD, 3.915% for PDZ, and 3.654% for VDZ. Non-glaucomatous intrasession ICC ranged from 0.711 to 0.824, non-glaucomatous intersession ICC ranged from 0.649 to 0.762, glaucomatous intrasession ICC ranged from 0.710 to 0.853, and glaucomatous intersession ICC ranged from 0.661 to 0.827. CONCLUSIONS: Macular OCTA scans can be a useful tool in monitoring the longitudinal progression of glaucoma due to their high repeatability and reproducibility.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY DETECTION OF BRUCH MEMBRANE AND CHORIOCAPILLARIS ABNORMALITIES IN SORSBY MACULAR DYSTROPHY.

PURPOSE: Swept-source optical coherence tomography angiography (SS-OCTA) was used to analyze Bruch membrane (BM) and choriocapillaris (CC) abnormalities in undiagnosed family members with Sorsby macular dystrophy (SMD). METHODS: In a family with SMD ( TIMP3 Tyr191Cys), SS-OCTA imaging was performed using the 6 × 6 mm scan patter and previously validated algorithms to detect abnormalities in BM and the CC, as well as the presence of reticular pseudodrusen and macular neovascularization. Genetic analyses were performed for TIMP3 mutations. RESULTS: Of eight family members, two were previously diagnosed with SMD and six were asymptomatic. SS-OCTA imaging of the 33-year-old proband revealed type 1 macular neovascularization in the left eye and bilateral reticular pseudodrusen, thickening of BM, CC thinning, and increases in CC flow deficits. A TIMP3 mutation was confirmed. His niece, despite having no clinical evidence of SMD, showed BM thickening and CC thinning on SS-OCTA. A TIMP3 mutation was confirmed. The proband's younger nephew and niece also carried the TIMP3 mutation without clinical evidence of SMD. Two additional members had normal examinations, unremarkable SS-OCTA findings, and no TIMP3 mutation. CONCLUSION: Swept-source optical coherence tomography angiography imaging can detect BM and CC abnormalities in vivo in subjects unaware of their TIMP3 status in a family with SMD.

Automatic geographic atrophy segmentation using optical attenuation in OCT scans with deep learning.

A deep learning algorithm was developed to automatically identify, segment, and quantify geographic atrophy (GA) based on optical attenuation coefficients (OACs) calculated from optical coherence tomography (OCT) datasets. Normal eyes and eyes with GA secondary to age-related macular degeneration were imaged with swept-source OCT using 6 × 6 mm scanning patterns. OACs calculated from OCT scans were used to generate customized composite en face OAC images. GA lesions were identified and measured using customized en face sub-retinal pigment epithelium (subRPE) OCT images. Two deep learning models with the same U-Net architecture were trained using OAC images and subRPE OCT images. Model performance was evaluated using DICE similarity coefficients (DSCs). The GA areas were calculated and compared with manual segmentations using Pearson's correlation and Bland-Altman plots. In total, 80 GA eyes and 60 normal eyes were included in this study, out of which, 16 GA eyes and 12 normal eyes were used to test the models. Both models identified GA with 100% sensitivity and specificity on the subject level. With the GA eyes, the model trained with OAC images achieved significantly higher DSCs, stronger correlation to manual results and smaller mean bias than the model trained with subRPE OCT images (0.940 ± 0.032 vs 0.889 ± 0.056, p = 0.03, paired t-test, r = 0.995 vs r = 0.959, mean bias = 0.011 mm vs mean bias = 0.117 mm). In summary, the proposed deep learning model using composite OAC images effectively and accurately identified, segmented, and quantified GA using OCT scans.

Capillary density and caliber as assessed by optical coherence tomography angiography may be significant predictors of diabetic retinopathy severity.

PURPOSE: To validate retinal capillary density and caliber associations with diabetic retinopathy (DR) severity in different clinical settings. METHODS: This cross-sectional study assessed retinal capillary density and caliber in the superficial retinal layer of 3-mm OCTA scans centered on the fovea. Images were collected from non-diabetic controls and subjects with mild or referable DR (defined DR worse than mild DR) between February 2016 and December 2019 at secondary and tertiary eye care centers. Vessel Skeleton Density (VSD), a measure of capillary density, and Vessel Diameter Index (VDI), a measure of vascular caliber, were calculated from these images. Discriminatory performance of VSD and VDI was evaluated using multivariable logistic regression models predicting DR severity with adjustments for sex, hypertension, and hyperlipidemia. Area under the curve (AUC) was estimated. Model performance was evaluated in two different cohorts. RESULTS: This study included 594 eyes from 385 subjects. Cohort 1 was a training cohort of 509 eyes including 159 control, 155 mild non-proliferative DR (NPDR) and 195 referable DR eyes. Cohort 2 was a validation cohort consisting of 85 eyes including 16 mild NPDR and 69 referable DR eyes. In Cohort 1, addition of VSD and VDI to a model using only demographic data significantly improved the model's AUC for discrimination of eyes with any DR severity from controls (0.91 [95% CI, 0.88-0.93] versus 0.80 [95% CI, 0.76-0.83], p < 0.001) and eyes with referable DR from mild NPDR (0.90 [95% CI, 0.86-0.93] versus 0.69 [95% CI, 0.64-0.75], p < 0.001). The transportability of this regression model was excellent when implemented in Cohort 2 for the referable DR versus mild NPDR comparison. The odds ratio of having any DR compared to control subjects, and referable DR compared to mild DR decreased by 15% (95% CI: 12-18%), and 13% (95% CI: 10-15%), respectively, for every 0.001 unit increase in VSD after adjusting for comorbidities. CONCLUSION: OCTA-derived capillary density has real world clinical value for rapidly assessing DR severity.

Optical Coherence Tomography Measurements of the Retinal Pigment Epithelium to Bruch Membrane Thickness Around Geographic Atrophy Correlate With Growth.

PURPOSE: The retinal pigment epithelium (RPE) to Bruch membrane (BM) distance around geographic atrophy (GA) was measured using an optical attenuation coefficient (OAC) algorithm to determine whether this measurement could serve as a clinical biomarker to predict the annual square root enlargement rate (ER) of GA. DESIGN: A retrospective analysis of a prospective, observational case series. METHODS: Eyes with GA secondary to age-related macular degeneration (AMD) were imaged with swept-source OCT (SS-OCT) using a 6 × 6-mm scan pattern. GA lesions were identified and measured using customized en face OCT images, and GA annual square root ERs were calculated. At baseline, the OACs were calculated from OCT datasets to generate customized en face OAC images for GA visualization. RPE-BM distances were measured using OAC data from different subregions around the GA. RESULTS: A total of 38 eyes from 27 patients were included in this study. Measured RPE-BM distances were the highest in the region closest to GA. The RPE-BM distances immediately around the GA were significantly correlated with GA annual square root ERs (r = 0.595, P < .001 for a 0- to 300-µm rim around the GA). No correlations were found between RPE-BM distances and previously published choriocapillaris (CC) flow deficits in any subregions. CONCLUSIONS: RPE-BM distances from regions around the GA significantly correlate with the annual ERs of GA. These results suggest that an abnormally thickened RPE/BM complex contributes to GA growth and that this effect is independent of CC perfusion deficits.

Analysis of correlations between local geographic atrophy growth rates and local OCT angiography-measured choriocapillaris flow deficits.

The purpose of this study is to quantitatively assess correlations between local geographic atrophy (GA) growth rates and local optical coherence tomography angiography (OCTA)-measured choriocapillaris (CC) flow deficits. Thirty-eight eyes from 27 patients with GA secondary to age-related macular degeneration (AMD) were imaged with a commercial 1050 nm swept-source OCTA instrument at 3 visits, each separated by ∼6 months. Pearson correlations were computed between local GA growth rates, estimated using a biophysical GA growth model, and local OCTA CC flow deficit percentages measured along the GA margins of the baseline visits. The p-values associated with the null hypothesis of no Pearson correlation were estimated using a Monte Carlo permutation scheme that incorporates the effects of spatial autocorrelation. The null hypothesis (Pearson's ρ = 0) was rejected at a Benjamini-Hochberg false discovery rate of 0.2 in 15 of the 114 visit pairs, 11 of which exhibited positive correlations; even amongst these 11 visit pairs, correlations were modest (r in [0.30, 0.53]). The presented framework appears well suited to evaluating other potential imaging biomarkers of local GA growth rates.

Optical Coherence Tomography Angiography-Derived Flux As a Measure of Physiological Changes in Retinal Capillary Blood Flow.

Purpose: To compare optical coherence tomography angiography (OCTA)-derived flux with conventional OCTA measures of retinal vascular density in assessment of physiological changes in retinal blood flow. Methods: Healthy subjects were recruited, and 3 × 3-mm2 fovea-centered scans were acquired using commercially available swept-source OCTA (SS-OCTA) while participants were breathing room air, 100% O2, or 5% CO2. Retinal perfusion was quantified using vessel area density (VAD) and vessel skeleton density (VSD), as well as novel measures of retinal perfusion, vessel area flux (VAF) and vessel skeleton flux (VSF). Flux is proportional to the number of red blood cells moving through a vessel segment per unit time. The percentage change in each measure was compared between the O2 and CO2 gas conditions for images of all vessels (arterioles, venules, and capillaries) and capillary-only images. Statistical significance was determined using paired t-tests and a linear mixed-effects model. Results: Eighty-four OCTA scans from 29 subjects were included (age, 45.9 ± 19.5 years; 14 male, 48.3%). In capillary-only images, the change under the CO2 condition was 168% greater in VAF than in VAD (P = 0.002) and 124% greater in VSF than in VSD (P = 0.004). Similarly, under the O2 condition, the change was 94% greater in VAF than in VAD (P = 0.004) and 57% greater in VSF than in VSD (P = 0.01). Flux measures showed significantly greater change in capillary-only images compared with all-vessels images. Conclusions: OCTA-derived flux measures quantify physiological changes in retinal blood flow at the capillary level with a greater effect size than conventional vessel density measures. Translational Relevance: OCTA-derived flux is a useful measure of subclinical changes in retinal capillary perfusion.