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Purpose: To introduce a novel method for assessment of retinal vasculitis using swept-source OCT angiography (SS-OCTA)., Design: Retrospective case series., Participants: Patients with retinal vasculitis., Methods: The subjects were identified among the clinic population and imaged with 12 × 12-mm SS-OCTA scans centered on the fovea. A custom retina segmentation superimposed the color retinal thickness map on a modified en face flow scan. Findings from en face flow scans were correlated with localized perivascular retinal thickening on B-scans. Results from SS-OCTA were compared with fluorescein angiography (FA) to examine the proportion of perivascular thickening to retinal vascular leakage or staining., Results: Twenty-one patients with retinal vasculitis underwent same-day FA and SS-OCTA. Visible retinal vascular leakage/staining on FA corresponded to increased perivascular retinal thickness on SS-OCTA in 17 patients. Five patients had a second examination with same-day FA and SS-OCTA after treatment of the vasculitis. Three of those 5 patients showed improved retinal vascular leakage/staining on post-treatment FA and decreased perivascular retinal thickness on SS-OCTA scans., Conclusions: Swept-source OCT angiography detects structural retinal thickening secondary to inflammatory retinal vascular leakage. Further studies are required to confirm whether SS-OCTA may serve as a semiquantitative alternative to FA to diagnose and monitor the response to treatment in patients with retinal vasculitis., (Published by Elsevier Inc.)

Purpose: To investigate the characteristics of treatment-naïve nonexudative macular neovascularization (MNV) in age-related macular degeneration before the onset of exudation using swept-source optical coherence tomography angiography., Methods: MNV area, choriocapillaris (CC) flow deficits (FDs), vessel area density (VAD), vessel skeleton density (VSD), retinal pigment epithelial detachment (PED) volume, mean choroidal thickness (MCT), and choroid vascularity index (CVI) measurements were assessed at two visits prior to exudation. We compared measurements made at the second visit and the rate of change between visits in eyes with and without exudation. The differences in these parameters between eyes with and without subsequent exudation were summarized with 95% confidence intervals (CIs)., Results: Twenty-one eyes with nonexudative MNV were identified and followed. Nine eyes developed exudation, and 12 eyes did not develop exudation. Differences between these groups of eyes for all parameters tended to be small, and the 95% CIs largely ruled out any substantial differences. Overall, eyes with exudation had 24% smaller VAD, 20% smaller VSD, and 33% smaller PED volume measurements. No noteworthy differences were observed for MNV area, CC FDs, MCT, or CVI measurements., Conclusions: The onset of exudation was correlated with lesions having less vascularity and smaller PED volume measurements, but measurements of MNV area, CC FDs, MCT, and CVI were not correlated with near-term exudation. Investigations are ongoing to further explore these and other anatomic changes as harbingers of near-term exudation.

Purpose: We compared the ability of ophthalmologists to identify neovascularization (NV) in patients with proliferative diabetic retinopathy using swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA)., Design: Retrospective study comparing diagnostic instruments., Methods: Eyes with proliferative diabetic retinopathy or severe nonproliferative diabetic retinopathy and a high suspicion of NV based on clinical examination were imaged using SS-OCTA and FA at the same visit. Two separate grading sets consisting of scrambled, anonymized SS-OCTA and FA images were created. The ground truth for presence of NV was established by consensus of 2 graders with OCTA experience who did not participate in the subsequent assessment of NV in this study. The 2 anonymized image sets were graded for presence or absence of NV by 12 other graders that included 2 residents, 6 vitreoretinal fellows, and 4 vitreoretinal attending physicians. The percentage of correct grading of NV using SS-OCTA and FA was assessed for each grader and across grader training levels., Results: Forty-seven eyes from 24 patients were included in this study. Overall, the mean percentage of correct NV grading was 87.8% using SS-OCTA with B-scans and 86.2% using FA (P = .92). Assessing each grader individually, there was no statistically significant asymmetry in correct grading using SS-OCTA and FA., Conclusions: Ophthalmologists across training levels were able to identify diabetic NV with equal accuracy using SS-OCTA and FA. Based on these results, SS-OCTA may be an appropriate standalone modality for diagnosing diabetic NV., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The hallmark of proliferative diabetic retinopathy (PDR) is retinal neovascularization. Tortuous intraretinal vascular segments known as intraretinal microvascular abnormalities (IRMAs) are a known risk factor for neovascularization (NV), but whether IRMA represents a biomarker or a vascular precursor lesion to NV has not been demonstrated. The purpose of this study was to determine whether IRMA may evolve directly into NV., Design: Retrospective analysis of prospective, observational case series., Participants: Patients with treatment-naïve PDR., Methods: Patients were imaged longitudinally with fluorescein angiography (FA) and swept-source (SS) OCT angiography (OCTA) before and after panretinal photocoagulation (PRP)., Main Outcome Measures: Presence and colocalization of IRMA and NV on serial FA and SS OCTA., Results: Two PDR patients showed multiple NV and IRMA lesions at baseline examination. Three months after PRP, FA demonstrated profuse leakage from 3 new NV lesions in one patient and 1 new NV lesion in another patient. Multimodal imaging showed that these 4 lesions were IRMAs at baseline. Swept-source OCTA performed before PRP and 1 week, 1 month, and 3 months after PRP confirmed that the precursor IRMA lesions were intraretinal tortuous vascular lesions at baseline and that they developed into preretinal NV with contiguous intraretinal components. NV was found to develop and adhere to the posterior hyaloid even in areas of pre-existing hyaloidal detachment., Conclusions: Diabetic retinal NV can develop from IRMA. Early identification of IRMAs may be an accurate means of predicting progression to PDR, and frequent monitoring of IRMAs with SS OCTA may facilitate early diagnosis of PDR., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Widefield swept source optical coherence tomography angiography (WF SS-OCTA) imaging was compared with ultra-widefield (UWF) fluorescein angiography (FA) imaging to better understand changes in retinal nonperfusion before and after panretinal photocoagulation (PRP) in treatment-naïve eyes with proliferative diabetic retinopathy (PDR)., Design: Prospective, observational, consecutive case series., Methods: Participants with treatment-naïve PDR were imaged using the SS-OCTA 12- × 12-mm scan pattern at baseline and at 1 week, 1 month, and 3 months after PRP. UWF FA was obtained at baseline and 3 months after PRP. Selected eyes were imaged using 5 SS-OCTA 12- × 12-mm scans to create a posterior pole montage, and 5 eyes also underwent SS-OCTA imaging at 6 months and 1 year. Areas of retinal nonperfusion (RNP) were drawn independently by 2 masked graders, and analysis of variance (ANOVA) tests were used to compare areas of RNP over time. Main outcome measurements consisted of areas and boundaries of RNP visualized using WF SS-OCTA and UWF FA., Results: From January 2018 through January 2019, WF SS-OCTA was performed on 20 eyes with treatment-naïve PDR from 15 patients. Areas of RNP identified on UWF FA images co-localized with RNP areas visualized on WF SS-OCTA images. There were no statistically significant changes in RNP area on WF SS-OCTA images through 3 months after PRP. Even eyes that were severely ischemic at baseline had no significant changes in RNP area 1 year after PRP., Conclusions: RNP in PDR can be identified at baseline and imaged serially after PRP using WF SS-OCTA. Retinal perfusion in PDR does not change significantly after PRP. The ability of WF SS-OCTA to longitudinally evaluate RNP areas provides additional justification for adopting WF SS-OCTA as the sole imaging modality for clinical management of PDR., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To determine age-related changes in choroidal thickness and the volume of choroidal vessels and stroma using automated algorithms based on structural swept-source OCT (SS-OCT) scans., Design: Prospective and observational study., Participants: The study included 144 normal participants with ages ranging from 20 to 88 years., Methods: A previously reported strategy was used to automatically segment the choroid using SS-OCT structural images. Attenuation correction was applied on B-scans to enhance the choroidal contrast and facilitate more accurate automatic segmentation of the 3-dimensional choroidal vessel and stroma. The parameters that we investigated included mean choroidal thickness (MCT), choroidal vessel volume (CVV), choroidal stroma volume (CSV), choroid vascularity index (CVI), and the choroidal stroma-to-vessel volume ratio (CSVR). Correlations between MCT and choroidal vessel metrics of CVV, CSV, CVI, and CSVR were studied. Regional distributions of MCT and CVI were analyzed using a grid centered on the fovea. Age-related changes in MCT, CVV, CSV, and CVI were studied in the entire scanning region, as well as in the subregions of the grids., Main Outcome Measures: Age-related changes in MCT, CVV, CSV, and CVI using 6×6-mm and 12×12-mm SS-OCT scans., Results: The automated choroid segmentations were validated against manual segmentations, and MCT measurements were shown to be in good agreement (P < 0.0001). Choroidal vessel volume and CSV showed significant correlations with MCT (all P < 0.0001). Interestingly, CVI and CSVR were constant, with little variation among all participants regardless of age and MCT (61.1±1.8% and 0.64±0.05, respectively). Measurements on 12×12-mm and 6×6-mm scans showed excellent agreement in all scan regions (all P < 0.0001). While choroidal thickness and choroidal volume, which includes both choroidal vessels and stroma, decrease with age (all P < 0.0001), the CVI and CSVR vary little among all ages in all regions., Conclusions: Whereas MCT, CVV, and CSV decrease with age, the CVI and CSVR remain constant in all regions with age. Ongoing studies are using these automated algorithms on SS-OCT structural datasets to investigate the diagnostic usefulness of these choroidal parameters in a myriad of ocular and systemic diseases., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the possible correlation between the annual enlargement rates (ERs) of geographic atrophy (GA) with the percentage and size of the choriocapillaris (CC) flow deficits (FDs) surrounding GA, measured with swept-source OCT angiography (SS-OCTA) images., Design: Prospective, observational case series., Participants: Patients with GA secondary to nonexudative AMD., Methods: Patients were imaged with a 100-kHz SS-OCTA instrument (PLEX Elite 9000, Carl Zeiss Meditec, Dublin, CA) using a 6×6-mm field of view scan pattern. The GA area measurements were obtained from en face SS-OCT sub-retinal pigment epithelium (RPE) slab images. Visualization of the CC and quantification of FDs were performed using a previously published validated algorithm based on a 20-μm thickness slab with the inner boundary located beneath Bruch's membrane. The percentage of CC FDs (FD%) and the average FD area measurements were calculated in different regions around the GA., Main Outcome Measures: The correlation between the CC FDs and the ERs of GA., Results: Twenty-two eyes from 15 patients were eligible for the analysis. The annual square root ERs for GA ranged from 0.07 to 0.75 mm/year. The CC FD% and average FD area measurements were highly correlated with each other (P < 0.001), with the highest FD values found in the region closest to the margin of GA. The ERs correlated best with the average CC FD area measurements in the total scan area minus the area of GA (Pearson r = 0.747; P < 0.001) than those in the regions immediately surrounding the GA (r = 0.544; P = 0.009)., Conclusions: Contrary to expectations, the global CC FD measurements had a better correlation with the ERs of GA than those in the regions immediately around the GA. The most likely explanation for this outcome is that normal age-related increases in FDs within the central macula confound the correlations between the ERs of GA and FDs, whereas the regions furthest away from the margins of GA are less affected by normal age-related changes and reflect FD alterations related to AMD severity., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: Wide-field swept-source (SS) OCT angiography (OCTA) was compared with ultrawide-field (UWF) fluorescein angiography (FA) for evaluating neovascularization (NV) before and after panretinal photocoagulation (PRP) in eyes with treatment-naive proliferative diabetic retinopathy (PDR)., Design: Prospective, observational, consecutive case series., Participants: Patients with treatment-naive PDR., Methods: Patients were imaged using the SS OCTA 12 × 12-mm field of view (PLEX Elite 9000; Carl Zeiss Meditec, Inc, Dublin, CA) at baseline and at 1 week, 1 month, and 3 months after PRP. Select eyes were imaged with 5 SS OCTA 12 × 12-mm scans to create posterior pole montages. Ultrawide-field fundus photography and UWF FA were obtained at baseline and 3 months after PRP., Main Outcome Measures: Neovascularization visualized using wide-field SS OCTA and UWF FA., Results: From January through May 2018, wide-field SS OCTA was performed on 20 eyes with treatment-naive PDR from 15 patients. The en face SS OCTA 12 × 12-mm vitreoretinal interface (VRI) slab images showed NV at baseline in 18 of 20 eyes (90%). Of the remaining 2 eyes, the posterior pole montage captured peripheral NV in one eye, and in the other eye, no evidence of NV was detected with either UWF FA or SS OCTA. After PRP, both SS OCTA and FA demonstrated similar progression or regression of NV, but SS OCTA provided more detailed visualization of the vascular changes., Conclusions: Neovascularization in PDR can be identified at baseline and imaged serially after PRP using wide-field SS OCTA. In patients with a high clinical suspicion for PDR, wide-field SS OCTA likely will be the only imaging method needed for diagnosis and longitudinal evaluation of NV., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The goal of this study was to determine the retinal blood flow rate (BFR) and blood flow velocity (BFV) of pre-capillary arterioles and post-capillary venules in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Forty patients (20 AD and 20 MCI) and 21 cognitively normal (CN) controls with a similar age range (± 5 yrs) were recruited. A retinal function imager (RFI) was used to measure BFRs and BFVs of arterioles and venules in the macular region. The thickness of the ganglion cell-inner plexiform layer (GCIPL) was measured using Zeiss Cirrus optical coherence tomography. Macular BFRs in AD group were 2.64 ± 0.20 nl/s (mean ± standard deviation) in arterioles and 2.23 ± 0.19 nl/s in venules, which were significantly lower than in MCI and CN groups (P < 0.05). In addition, BFRs in MCI were lower than in CN in both arterioles and venules (P < 0.05). The BFV of the arterioles was 3.20 ± 1.07 mm/s in AD patients, which was significantly lower than in CN controls (3.91 ± 0.77 mm/s, P = 0.01). The thicknesses of GCIPL in patients with AD and MCI were significantly lower than in CN controls (P < 0.05). Neither BFV nor BFR in arterioles and venules was related to age, GCIPL thickness, mini mental state examination (MMSE) score and disease duration in patients with AD and MCI (P > 0.05). The lower BFR in both arterioles and venules in AD and MCI patients together with the loss of GCIPL were evident, indicating the impairment of the two components in the neurovascular-hemodynamic system, which may play a role in disease progression.

Purpose: To characterize age-related alterations in the retinal microcirculation, microvascular network, and microstructure in healthy subjects., Methods: Seventy-four healthy subjects aged from 18 to 82 years were recruited and divided into four age groups (G1 with age <35 years, G2 with age 35 ∼ 49 years, G3 with age 50 ∼ 64 years, and G4 with age ≥65 years). Custom ultra-high resolution optical coherence tomography (UHR-OCT) was used to acquire six intraretinal layers of the macula. OCT angiography (OCTA) was used to image the retinal microvascular network. The retinal blood flow velocity (BFV) was measured using a Retinal Function Imager (RFI)., Results: Compared to G1, G2 had significant thinning of the retinal nerve fiber layer (RNFL) (P < 0.05), while G3 had thinning of the RNFL and ganglion cell and inner plexiform layer (GCIPL) (P < 0.05), in addition to thickening of the outer plexiform layer (OPL) and photoreceptor layer (PR) (P < 0.05). G4 had loss in retinal vessel density, thinning in RNFL and GCIPL, and decrease in venular BFV, in addition to thickening of the OPL and PR (P < 0.05). Age was negatively related to retinal vessel densities, the inner retinal layers, and venular BFV (P < 0.05). By contrast, age was positively related to OPL and PR (P < 0.05)., Conclusions: During aging, decreases in retinal vessel density, inner retinal layer thickness, and venular BFV were evident and impacted each other as observed by simultaneous changes in multiple retinal components.