Genetic susceptibility to schizophrenia through neuroinflammatory pathways is associated with retinal thinning: Findings from the UK-Biobank.

The human retina is part of the central nervous system and can be easily and non-invasively imaged with optical coherence tomography. While imaging the retina may provide insights on central nervous system-related disorders such as schizophrenia, a typical challenge are confounders often present in schizophrenia which may negatively impact retinal health. Here, we therefore aimed to investigate retinal changes in the context of common genetic variations conveying a risk of schizophrenia as measured by polygenic risk scores. We used population data from the UK Biobank, including White British and Irish individuals without diagnosed schizophrenia, and estimated a polygenic risk score for schizophrenia based on the newest genome-wide association study (PGC release 2022). We hypothesized that greater genetic susceptibility to schizophrenia is associated with retinal thinning, especially within the macula. To gain additional mechanistic insights, we conducted pathway-specific polygenic risk score associations analyses, focusing on gene pathways that are related to schizophrenia. Of 65484 individuals recruited, 48208 participants with available matching imaging-genetic data were included in the analysis of whom 22427 (53.48%) were female and 25781 (46.52%) were male. Our robust principal component regression results showed that polygenic risk scores for schizophrenia were associated with retinal thinning while controlling for confounding factors (b = -0.03, p = 0.007, pFWER = 0.01). Similarly, we found that polygenic risk for schizophrenia specific to neuroinflammation gene sets revealed significant associations with retinal thinning (b = -0.03, self-contained p = 0.041 (reflecting the level of association), competitive p = 0.05 (reflecting the level of enrichment)). These results go beyond previous studies suggesting a relationship between manifested schizophrenia and retinal phenotypes. They indicate that the retina is a mirror reflecting the genetic complexities of schizophrenia and that alterations observed in the retina of individuals with schizophrenia may be connected to an inherent genetic predisposition to neurodegenerative aspects of the condition. These associations also suggest the potential involvement of the neuroinflammatory pathway, with indications of genetic overlap with specific retinal phenotypes. The findings further indicate that this gene pathway in individuals with a high polygenic risk for schizophrenia could contribute through acute-phase proteins to structural changes in the retina.

Recurrent Blood Pressure Rise after Treatment with Anti-vascular Endothelial Growth Factor Agents.

BACKGROUND: It has previously been shown that the process of anti-vascular endothelial growth factor (VEGF) injections can lead to a significant increase of blood pressure. The aim of this study was to investigate whether this blood pressure increase was reproducible with repeated anti-VEGF injections. PATIENTS AND METHODS: Patients with a systolic blood pressure of ≥ 180 mmHg during previous injections who were scheduled for further injections were asked to participate in this study. Systolic as well as diastolic blood pressure was measured before, during, and after the intravitreal injection process. RESULTS: Thirty-nine patients (21 females, 18 males) with a mean age of 75 years (range 34 - 94 years) were included in this extension of the FEAR study. At first, clinical systolic blood pressure rose from an average of 157.3 ± 5.9 mmHg to 175 ± 6.7 mmHg at the time of the injection process (p < 0.01). Diastolic blood pressure rose from an average of 75.72 ± 4.2 mmHg to 84.44 ± 7.3 mmHg (p < 0.13) at the time of the injection process. Overall, the majority of the participants (56%, N = 22) had a systolic blood pressure of ≥ 180 mmHg. CONCLUSIONS: Our results show that the blood pressure increase occurs persistently during the injection process in some patients. Repeated episodes of severe hypertension may predispose patients to cardiovascular events, especially those with concomitant cardiovascular risk factors.

Evaluation of different Swept'Source optical coherence tomography angiography (SS-OCTA) slabs for the detection of features of diabetic retinopathy.

PURPOSE: To compare different Swept-Source optical coherence tomography angiography (SS-OCTA) slabs for the detection of features of diabetic retinopathy (DR), to find the most suitable slab for grading. METHODS: Retrospective cross-sectional study. Consecutive patients with DR were evaluated using SS-OCTA. The central 12 × 12 mm scan was used to generate the retinal, superficial and deep slab. The grading results of the slabs were then compared to determine if one specific slab is superior to detect respective features. RESULTS: A total of 348 eyes (190 patients; mean age 58.1 ± 14.5 years) were graded for features of DR. The retinal slab detected most frequently MAs and IRMAs, however with no significant difference compared to the superficial slab (p = 0.93 and p = 0.93, respectively). Small capillary dropout was most frequently found on the superficial slab, but there was no significant difference compared with the retinal (p = 0.78) and deep slab (p = 0.45). The only statistically significant difference was found for large capillary dropout, where the retinal and superficial slab showed a higher detection rate compared with the deep slab (p ≤ 0.0001 and p = 0.001, respectively). CONCLUSIONS: The superficial and retinal slabs are equally suitable for grading with no statistically significant difference in the detection rate of the diabetic features examined.

Repeatability of Wide-field Optical Coherence Tomography Angiography in Normal Retina.

PURPOSE: We evaluated the repeatability of wide-field en face swept-source optical coherence tomography angiography (SS-OCTA) in healthy subjects. METHODS: Healthy subjects underwent two imaging sessions, on average 8 days apart, with a 100 kHz SS-OCTA instrument. The imaging protocol included a central 3 × 3 and 12 × 12 mm scans of the four quadrants resulting in more than a 70° wide-field OCTA of the posterior pole. Quantitative analysis was performed using the inbuilt Macular Density Algorithm Version v0.6.1 and AngioTool software. Consistency for the foveal avascular zone (FAZ), vessel density, and perfusion density of the superficial and deep capillary plexus slabs and the wide-field OCTA superficial slab, and the number of artefacts on the wide-field images were assessed. RESULTS: A total of 21 healthy volunteers (seven men and 14 women; mean age 32 years; range, 18-61; standard deviation, 10.28 years) were included in this analysis. Internal consistency was highest for FAZ area with an intraclass correlation (ICC) = 0.998 (95% confidence interval [CI], 0.997-0.999), a FAZ perimeter with an ICC = 0.995 (95% CI, 0.990-0.997), a FAZ circularity with an ICC= 0.976 (95% CI, 0.956-0.987), followed by the vessel density of the inner ring in the superficial slab with an ICC = 0.834 (95% CI, 0.691-0.911), and a vessel density of the inner ring in the deep slab with an ICC = 0.523 (95% CI, 0.113-0.744).The reproducibility of the average vessels length of the wide-field OCTA cropped images was strong (ICC = 0.801; 95% CI, 0.624-0.895), followed by the reproducibility of total number of junctions (ICC = 0.795; 95% CI, 0.613-0.892) and the vessels percentage area (ICC = 0.662; 95% CI, 0.361-0.821). CONCLUSIONS: The level of reproducibility for assessing the microvascular anatomy in wide-field OCTA is strong and can be used to quantify microvascular changes over time. Refinements in analysis strategies and a consensus of which parameters are most useful for quantitative assessment of wide-field OCTA images would be useful in the future. TRANSLATIONAL RELEVANCE: These findings bridge the gap between basic imaging research and clinical use for quantitative wide-field OCTA.

Comparison of Choroidal Thickness Measurements Using Spectral Domain Optical Coherence Tomography in Six Different Settings and With Customized Automated Segmentation Software.

PURPOSE: We investigate which spectral domain-optical coherence tomography (SD-OCT) setting is superior when measuring subfoveal choroidal thickness (CT) and compared results to an automated segmentation software. METHODS: Thirty patients underwent enhanced depth imaging (EDI)-OCT. B-scans were extracted in six different settings (W+N = white background/normal contrast 9; W+H = white background/maximum contrast 16; B+N = black background/normal contrast 12; B+H = black background/maximum contrast 16; C+N = Color-encoded image on black background at predefined contrast of 9, and C+H = Color-encoded image on black background at high/maximal contrast of 16), resulting in 180 images. Subfoveal CT was manually measured by nine graders and by automated segmentation software. Intraclass correlation (ICC) was assessed. RESULTS: ICC was higher in normal than in high contrast images, and better for achromatic black than for white background images. Achromatic images were better than color images. Highest ICC was achieved in B+N (ICC = 0.64), followed by B+H (ICC = 0.54), W+N, and W+H (ICC = 0.5 each). Weakest ICC was obtained with Spectral-color (ICC = 0.47). Mean manual CT versus mean computer estimated CT showed a correlation of r = 0.6 (P = 0.001). CONCLUSION: Black background with white image at normal contrast (B+N) seems the best setting to manually assess subfoveal CT. Automated assessment of CT seems to be a reliable tool for CT assessment. TRANSLATIONAL RELEVANCE: To define optimized OCT analysis settings to improve the evaluation of in vivo imaging.

VASCULAR ABNORMALITIES IN DIABETIC RETINOPATHY ASSESSED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WIDEFIELD IMAGING.

PURPOSE: To detect vascular abnormalities in diabetic retinopathy using swept-source optical coherence tomography angiography (SS-OCTA) widefield images, and to compare the findings with color fundus photographs (CFPs) using Early Treatment Diabetic Retinopathy Study severity grading. METHODS: 3 mm × 3 mm and 12 mm × 12 mm scans were acquired to cover 70° to 80° of the posterior pole using a 100-kHz SS-OCTA instrument. Two masked graders assessed the presence of vascular abnormalities on SS-OCTA and the Early Treatment Diabetic Retinopathy Study level on CFP. The grading results were then compared. RESULTS: A total of 120 diabetic eyes (60 patients) were imaged with the SS-OCTA instrument. Cohort 1 (91 eyes; SS-OCTA grading only) showed microaneurysms in 91% (n = 83), intraretinal microvascular abnormalities in 79% (n = 72), and neovascularization in 21% (n = 19) of cases. Cohort 2 (52 eyes; CFP grading compared with SS-OCTA) showed microaneurysms on CFP in 90% (n = 47) and on SS-OCTA in 96% (n = 50) of cases. Agreement in intraretinal microvascular abnormality detection was fair (k = 0.2). Swept-source optical coherence tomography angiography detected 50% of intraretinal microvascular abnormality cases (n = 26), which were missed on CFP. Agreement in detecting neovascularization was moderate (k = 0.5). CONCLUSION: Agreement in detection of diabetic retinopathy features on CFP and SS-OCTA varies depending on the vascular changes examined. Swept-source optical coherence tomography angiography shows a higher detection rate of intraretinal microvascular abnormalities (P = 0.039), compared with Early Treatment Diabetic Retinopathy Study grading.

Suspended Scattering Particles in Motion: A Novel Feature of OCT Angiography in Exudative Maculopathies.

OBJECTIVE: To characterize features of extra-vascular optical coherence tomography angiography (OCTA) signals corresponding to hyperreflective intraretinal fluid across various exudative maculopathies. DESIGN: Multicenter, retrospective, observational study. PARTICIPANTS: Eyes with various forms of exudative maculopathy including diabetic retinopathy (DR), retinal vein occlusion (RVO), and neovascular-age related macular degeneration (nvAMD). METHODS: Patients with extra-vascular OCTA signal identified on en face OCTA images were included in this study. This signal was readily distinguishable from projection artifacts. The regions with the extra-vascular motion signal on OCTA were named "Suspended Scattering Particles in Motion (SSPiM)." Depth-encoded, color, en face OCTA images (3mm × 3mm) centered on the fovea and their corresponding structural OCT scans were used to quantify features of SSPiM and its corresponding hyperreflective fluid. Longitudinal data were collected when available. MAIN OUTCOME MEASURES: Anatomic location, the association with hyperreflective material, changes in location and appearance of SSPiM over time, and replication of SSPiM OCTA signal in an in vitro phantom. RESULTS: Seventy-six eyes in 62 patients with various forms of exudative maculopathy were evaluated; 60 eyes with DR, 9 eyes with RVO, and 5 eyes nvAMD, 1 eye with macroaneurysm, and 1 eye with radiation retinopathy. Intraretinal accumulations of fluid with increased OCT signal intensity corresponded to regions of SSPiM in several exudative maculopathies. An in vitro phantom model demonstrates that particulate matter in suspension can generate similar OCTA signal. SSPiM showed an anatomic preference for vascular-avascular junctions. The hyperreflective fluid corresponding to SSPiM appeared more frequently in Henle's fiber layer (HFL) than the inner nuclear layer (INL) and was highly associated with hyperreflective material (HRM) found bordering the fluid. In five of eight longitudinal cases, the resolution of SSPiM resulted in the formation of confluent HRM. Clinically, this appeared as hard exudate on funduscopic images. CONCLUSIONS: Clinical data suggest that SSPiM is a novel imaging feature of retinal vascular diseases that was not appreciated prior to the use of OCTA. We characterized several novel features of SSPiM and demonstrated that at least in some cases it resolves with residual hard exudate.

Comparison Between Spectral-Domain and Swept-Source Optical Coherence Tomography Angiographic Imaging of Choroidal Neovascularization.

Purpose: The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA). Methods: Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 × 3- and 6 × 6-mm2 scans were obtained on both instruments. The 3 × 3-mm2 SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 × 6-mm2 SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 × 3-mm2 scans and twice in the 6 × 6-mm2 scans. Choroidal neovascularization was excluded if not fully contained within the 3 × 3-mm2 scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. Results: Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 × 3-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm2, respectively (P = 0.047). For the 6 × 6-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm2 (P = 0.003). Conclusions: The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 × 6-mm2 scans.

Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms.

Purpose: To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. Methods: Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography (OMAGC) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 µm below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. Results: Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (P = 0.61, paired t-test) and 6 × 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (P = 0.41, paired t-test) and 6 × 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (P = 0.011, paired sample t-test) and the 6 × 6-mm scans (P = 0.021, paired t-test). Conclusions: The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.

En Face Optical Coherence Tomography Imaging for the Detection of Nascent Geographic Atrophy.

PURPOSE: To determine if en face optical coherence tomography (OCT) imaging can identify nascent geographic atrophy (nGA) in eyes with intermediate age-related macular degeneration (iAMD). DESIGN: Retrospective observational case series. METHODS: Patients with iAMD from the COMPLETE study at the Bascom Palmer Eye Institute were evaluated to determine if nGA was present at baseline and at follow-up using high-density Spectralis OCT B-scans and en face OCT images from the Cirrus OCT instrument. If available, additional en face OCT images and B-scans were analyzed at follow-up times beyond the 52-week period. RESULTS: A total of 37 eyes (27 patients) were evaluated for at least 1 year using both B-scans and en face images. Two drusen suspicious for nGA at baseline were identified, but neither druse developed GA after 24 and 62 months of follow-up, respectively. Another druse displayed hypertransmission into the choroid at week 52 on B-scan imaging and was classified as nGA. En face OCT imaging identified this druse as a focal bright area. Drusen breakdown occurred during a follow-up of 39 months. CONCLUSIONS: En face OCT imaging appeared to be as useful as routine B-scan imaging for identifying areas suspicious for nGA in this population from the COMPLETE Study. Additional longitudinal follow-up of eyes with drusen is needed to determine if en face OCT imaging can replace the evaluation of individual B-scans for the detection of nGA.

Comparison between Widefield En Face Swept-Source OCT and Conventional Multimodal Imaging for the Detection of Reticular Pseudodrusen.

PURPOSE: The ability to detect reticular pseudodrusen (RPD)/subretinal drusenoid deposits (SDDs) using 12×12-mm widefield en face swept-source optical coherence tomography (SS-OCT) imaging was compared with conventional multimodal imaging (color, fundus autofluorescence (FAF), and infrared reflectance [IR] imaging) in eyes with nonexudative age-related macular degeneration (AMD). DESIGN: Cross-sectional study. PARTICIPANTS: Patients with nonexudative AMD were prospectively enrolled in an SS-OCT imaging study at the Bascom Palmer Eye Institute. METHODS: On the same day, all participants underwent color, FAF, and IR fundus imaging, as well as imaging with a prototype Zeiss 100 kHz SS-OCT instrument (Carl Zeiss Meditec Inc, Dublin, CA). Two masked graders assessed the presence, absence, or uncertainty of RPD/SDDs on conventional multimodal images and separately on 4 different SS-OCT en face images derived from the same volumetric dataset. The results from grading the conventional images and the SS-OCT en face images were compared. MAIN OUTCOME MEASURES: Agreement in the detection of RPD/SDDs using different imaging modalities. RESULTS: A total of 307 eyes (209 patients) were graded for the presence or absence of RPD/SDDs. The agreement between SS-OCT and multimodal imaging was 83%. The difference in RPD/SDD detection with either image modality was not statistically significant (P = 0.21). The sensitivity of SS-OCT in RPD/SDD detection was 83%, and when using conventional imaging, the sensitivity was 75%. When using SS-OCT imaging alone, 10% of RPD/SDD cases would be missed, and when using conventional imaging alone, 14% of RPD/SDD cases would be missed. The presence of RPD/SDD was confirmed retrospectively in 48 of 52 cases once the overall grading was unmasked and the graders reevaluated the conventional multimodal images and the widefield SS-OCT en face images. CONCLUSIONS: All 4 imaging modalities used together provided the best strategy for the detection of RPD/SDDs. However, when using widefield en face SS-OCT slab imaging alone, the detection of RPD/SDDs was at least as good as conventional imaging.

Choroidal Thickness and Choroidal Vessel Density in Nonexudative Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Imaging.

Purpose: To analyze the relationship between choroidal thickness and the distribution of choroidal blood vessels in eyes with nonexudative AMD. Methods: Eyes with a diagnosis of nonexudative AMD were imaged using a prototype 100-kHz swept-source (SS) optical coherence tomography (OCT) instrument (Carl Zeiss Meditec, Dublin, CA, USA) with a central wavelength of 1050 nm. We used an OCT cube scan pattern consisting of 512 × 512 A-scans over a 12 × 12 mm retinal area. The eyes were partitioned into two groups based on the presence or absence of reticular pseudodrusen (RPD). All scans were segmented using an automated algorithm. In addition, five eyes from each of the two groups were randomly chosen for manual segmentation. Binary choroidal vessels maps were generated from suitable OCT choroidal slabs, and the relationship between the density of large choroidal vessels and choroidal thickness was analyzed using an Early Treatment Diabetic Retinopathy Study-like target centered on the fovea. Results: Twenty-five eyes were enrolled in each group. The automated algorithm produced accurate choroidal thickness maps with an average difference between the manual and automated segmentations of 13.7 µm. There was a significant and stable correlation between choroidal thickness and choroidal vessel density across the two groups. Both average choroidal thickness and vessel density were significantly lower in eyes with RPD. Conclusions: Our fully automated choroidal segmentation algorithm was able to capture the different patterns of choroidal thickness over a wide area. Choroidal thickness has a clear relationship with the density of large choroid vessels in our sample, irrespective of the presence or absence of RPD.

Artifactual Flow Signals Within Drusen Detected by OCT Angiography.

BACKGROUND AND OBJECTIVE: To demonstrate possible flow artifacts when imaging drusen with optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: Patients with drusen were enrolled in a prospective OCT study using the Zeiss AngioPlex OCTA instrument (Carl Zeiss Meditec, Dublin, CA). Two kinds of en face slabs were created for visualizing both structure and flow. The first slab followed the contour of Bruch's membrane. The second slab had an inner boundary following the retinal pigment epithelium (RPE) contour and an outer boundary following the contour of Bruch's membrane. The structure and flow signals from within the drusen were compared. RESULTS: Eleven eyes of nine patients with age-related macular degeneration and drusen were imaged. In all 11 eyes, an artifactual flow signal was seen on the first slab where it intersected the RPE. This flow signal was a projection artifact from the overlying retinal vessels. The second slab did not show evidence of flow within drusen. CONCLUSION: OCTA decorrelation projection artifacts can be misinterpreted as apparent flow within drusen if the slab region includes hyperreflective boundary layers such as the RPE. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:517-522.].

Anatomic Clinical Trial Endpoints for Nonexudative Age-Related Macular Degeneration.

TOPIC: To review the role of anatomic endpoints in clinical trials for the study of nonexudative age-related macular degeneration (AMD) with an emphasis on a novel composite endpoint for the study of emerging therapies for intermediate AMD (iAMD). CLINICAL RELEVANCE: Unlike clinical trials for exudative AMD, it is impractical to use the change in visual acuity (VA) as a primary endpoint for the study of nonexudative AMD. By the time VA has been lost in nonexudative AMD, proof-of-concept early-stage clinical trials would take years to run, and drug development would be a near impossible task. Surrogate endpoints are needed that reliably predict future vision loss and can be easily measured. Anatomic changes that correlate with disease progression in nonexudative AMD offer the greatest promise as primary endpoints. METHODS: In preparation for this review, the electronic PubMed database was searched for relevant research pertaining to anatomic endpoints for the study of nonexudative AMD. Paper selection was based on our knowledge of the field with the goal to be as inclusive as possible. Whenever possible, recent review articles and results from large clinical trials, preferably with outcomes from many years of follow-up were favored over trials of short duration. RESULTS: The most commonly used anatomic endpoint for the study of late, nonexudative AMD is the growth of geographic atrophy (GA). The advantages of studying GA include the appreciation that its enlargement through the foveal center leads to significant vision loss through the availability of natural history studies, the understanding that prevention of this growth would preserve vision in the future, the ability to reliably measure GA using different imaging strategies, and the development appropriate statistical tools that reliably predict the growth of GA over time. The major disadvantage of using GA is that significant, irreversible disease progression has already occurred. The use of drusen volume as a predictor of disease progression and the use of a composite endpoint that incorporates drusen growth, formation of GA, and formation of neovascularization offers an opportunity to study therapies at an earlier stage of AMD with a greater likelihood of preserving better vision over a lifetime. CONCLUSIONS: Anatomic endpoints for the study of nonexudative AMD are needed to accelerate drug development, and the availability of optical coherence tomography algorithms capable of reliably measuring drusen morphology offer the best opportunity to study therapies for iAMD.

ZEISS Angioplex™ Spectral Domain Optical Coherence Tomography Angiography: Technical Aspects.

ZEISS Angioplex™ optical coherence tomography (OCT) angiography generates high-resolution three-dimensional maps of the retinal and choroidal microvasculature while retaining all of the capabilities of the existing CIRRUS™ HD-OCT Model 5000 instrument. Angioplex™ OCT angiographic imaging on the CIRRUS™ HD-OCT platform was made possible by increasing the scanning rate to 68,000 A-scans per second and introducing improved tracking software known as FastTrac™ retinal-tracking technology. The generation of en face microvascular flow images with Angioplex™ OCT uses an algorithm known as OCT microangiography-complex, which incorporates differences in both the phase and intensity information contained within sequential B-scans performed at the same position. Current scanning patterns for en face angiographic visualization include a 3 × 3 and a 6 × 6 mm scan pattern on the retina. A volumetric dataset showing erythrocyte flow information can then be displayed as a color-coded retinal depth map in which the microvasculature of the superficial, deep, and avascular layers of the retina are displayed together with the colors red, representing the superficial microvasculature; green, representing the deep retinal vasculature; and blue, representing any vessels present in the normally avascular outer retina. Each retinal layer can be viewed separately, and the microvascular layers representing the choriocapillaris and the remaining choroid can be viewed separately as well. In addition, readjusting the contours of the slabs to target different layers of interest can generate custom en face flow images. Moreover, each en face flow image is accompanied by an en face intensity image to help with the interpretation of the flow results. Current clinical experience with this technology would suggest that OCT angiography should replace fluorescein angiography for retinovascular diseases involving any area of the retina that can be currently scanned with the CIRRUS™ HD-OCT instrument and may replace fluorescein angiography and indocyanine green angiography for some choroidal vascular diseases.

Widefield En Face Optical Coherence Tomography Imaging of Subretinal Drusenoid Deposits.

BACKGROUND AND OBJECTIVE: To determine whether subretinal drusenoid deposits (SDD) can be detected on widefield en face slab images derived from spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) volume scans. PATIENTS AND METHODS: Retrospective study of patients with dry age-related macular degeneration (AMD) enrolled prospectively in an OCT imaging study using SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA) with a central wavelength of 840 nm, and a prototype 100-kHz SS-OCT instrument (Carl Zeiss Meditec) with a central wavelength of 1,050 nm. Seven en face slabs were evaluated with thicknesses from 20 to 55 µm and positioned at distances up to 55 µm above the retinal pigment epithelium (RPE). A montage of 6 × 6 mm SD-OCT en face images of the posterior pole from each patient was compared with a 9 × 12 mm SS-OCT single en face slab image and with color, autofluorescence, and infrared reflectance images. RESULTS: A total of 160 patients (256 eyes) underwent scanning with both OCT instruments; 57 patients (95 eyes) also underwent multimodal fundus imaging. Of 95 eyes, 32 (34%) were diagnosed with reticular pseudodrusen (RPD) using multimodal imaging. All eyes with RPD demonstrated a pattern of SDD on widefield en face OCT similar to that observed for RPD. The en face slab image that consistently identified SDD was the 20-µm thick slab with boundaries from 35 to 55 µm above the RPE. CONCLUSION: Widefield en face slab imaging with SD-OCT and SS-OCT can detect SDD and could replace multimodal imaging for the diagnosis of RPD in the future.

ASSOCIATION OF PREVASCULAR VITREOUS FISSURES AND CISTERNS WITH VITREOUS DEGENERATION AS ASSESSED BY SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To demonstrate the presence of prevascular vitreous fissures (PVF) and posterior vitreous cisterns in vivo and correlate with the degree of vitreous degeneration (VD). METHODS: This was a cross-sectional study using Topcon Deep Range Imaging OCT-1 Atlantis 3D swept source optical coherence tomography for acquiring scans of posterior vitreous covering an 18 × 18-mm area in 104 eyes of 52 healthy volunteers without posterior vitreous detachment. RESULTS: We observed that increasing age was associated with higher VD grades (P < 0.05). Prevascular vitreous fissures, characterized by areas of lower optical density overlying the retinal blood vessels, were identified in 93 (89%) eyes, and the presence of PVF correlated with lower VD grades (P < 0.05). Presence of cisterns correlated with higher VD grades (P < 0.05). All eyes with absence of PVF were found to have established cisterns. Prevascular vitreous fissures were connected with cisterns in 44 of the 71 (62%) eyes with cisterns, while the base of the cistern was directly above retinal blood vessels in 38 (54%) eyes, which suggests that the cisterns could be derived from PVF. CONCLUSION: Swept source optical coherence tomography imaging can identify PVF and cisterns occurring in the context of age-related VD, and PVF appeared to be possible precursors of cisterns.

OUTER RETINAL TUBULATION IN ADVANCED AGE-RELATED MACULAR DEGENERATION: Optical Coherence Tomographic Findings Correspond to Histology.

PURPOSE: To compare optical coherence tomography (OCT) and histology of outer retinal tubulation (ORT) secondary to advanced age-related macular degeneration in patients and in postmortem specimens, with particular attention to the basis of the hyperreflective border of ORT. METHOD: A private referral practice (imaging) and an academic research laboratory (histology) collaborated on two retrospective case series. High-resolution OCT raster scans of 43 eyes (34 patients) manifesting ORT secondary to advanced age-related macular degeneration were compared to high-resolution histologic sections through the fovea and superior perifovea of donor eyes (13 atrophic age-related macular degeneration and 40 neovascular age-related macular degeneration) preserved ≤4 hours after death. RESULTS: Outer retinal tubulation seen on OCT correlated with histologic findings of tubular structures consisted largely of cones lacking outer segments and lacking inner segments. Four phases of cone degeneration were histologically distinguishable in ORT lumenal walls, nascent, mature, degenerate, and end stage (inner segments and outer segments, inner segments only, no inner segments, and no photoreceptors and only Müller cells forming external limiting membrane, respectively). Mitochondria, which are normally long and bundled within inner segment ellipsoids, were small and scattered within shrunken inner segments and cell bodies of surviving cones. A lumenal border was delimited by an external limiting membrane. Outer retinal tubulation observed in closed and open configurations was distinguishable from cysts and photoreceptor islands on both OCT and histology. Hyperreflective lumenal material seen on OCT represents trapped retinal pigment epithelium and nonretinal pigment epithelium cells. CONCLUSION: The defining OCT features of ORT are location in the outer nuclear layer, a hyperreflective band differentiating it from cysts, and retinal pigment epithelium that is either dysmorphic or absent. Histologic and OCT findings of outer retinal tubulation corresponded in regard to composition, location, shape, and stages of formation. The reflectivity of ORT lumenal walls on OCT apparently does not require an outer segment or an inner/outer segment junction, indicating an independent reflectivity source, possibly mitochondria, in the inner segments.

The premacular bursa's shape revealed in vivo by swept-source optical coherence tomography.

OBJECTIVE: To resolve the controversy surrounding the shape and relationship of posterior vitreous spaces by characterizing the connections between the premacular bursa, the area of Martegiani, and Cloquet's canal. DESIGN: Comprehensive posterior vitreous maps were created using swept-source optical coherence tomography (SS OCT) in a cross-sectional study. PARTICIPANTS: The posterior vitreous of 102 eyes of 51 volunteers 21 to 54 years of age without ocular pathologic features was imaged using SS OCT. METHODS: The DRI OCT-1 Atlantis 3D SS OCT (Topcon Medical Systems, Oakland, NJ) was used to acquire scans of the posterior vitreous over an 18×18-mm area. MAIN OUTCOME MEASURES: Posterior vitreous spaces and their relationships were identified. RESULTS: The premacular bursa was identified in all 102 eyes and was found to extend superiorly beyond our scanning ability at a variable angle. No discernible superior borders could be identified. Instead, a connection of the bursa with the preoptic area of Martegiani or its extension, Cloquet's canal, was found in 101 of 102 eyes. This connection occurred at a variable distance from the optic nerve, where it formed a flat and broad superior channel. The skyward direction of this channel was found to be gravity dependent in all 14 eyes of the 7 subjects examined in various head positions. Although SS OCT was able to identify vitreous degeneration, the above changes were present in 28 eyes even without any discernible vitreous degeneration. CONCLUSIONS: The premacular bursa, also called the posterior precortical vitreous pocket, was found to continue superiorly beyond the posterior pole without a detectable border. The bursa fused broadly with the extension of the preoptic area of Martegiani, namely Cloquet's canal, or the hyaloidal tract of Eisner. These findings suggest that there is a direct anteroposterior connection between the retrolental and premacular and preoptic spaces already existent in the eyes of young adults before the occurrence of vitreous degeneration. This observation may have important implications with respect to the movement of intrinsic and extrinsic mediators between the anterior and posterior segments.