Faculty Bibliography

PURPOSE/OBJECTIVE:To investigate the association between choroidal caverns, choroidal vascular hyperpermeability (CVH), and pachyvessels in eyes with pachychoroid disease. METHODS:This was a retrospective review of swept-source optical coherence tomography and indocyanine green angiography imaging performed on eyes with pachychoroid disease. RESULTS:Imaging from 21 eyes with pachychoroid disease entities (8 eyes with pachychoroid pigment epitheliopathy, 11 eyes with central serous chorioretinopathy, and 3 eyes with pachychoroid neovasculopathy) from 11 patients (mean 49.5 years, male/female: 10/1, all white) was available for review. In all study eyes, pachyvessels traversed the areas of CVH visible in mid- and late-phase indocyanine green angiography. A total of 504 choroidal caverns were identified in 11 study eyes (52%). Of the 504 choroidal caverns, 445 (88%) were seen within the areas of CVH compared with 59 (12%), which were detected outside the areas of CVH (P < 0.001). Eyes with multiple caverns had an increased choroidal thickness when compared with eyes with ≤1 cavern (P < 0.001). CONCLUSION/CONCLUSIONS:Choroidal caverns, found primarily in the areas of indocyanine green angiography CVH traversed by pachyvessels, were detected in 52% of eyes with pachychoroid disease. The presence of choroidal caverns in these cases may indicate a loss of normal choroidal architecture associated with dilated Haller layer veins and increased choroidal thickness.

PURPOSE/OBJECTIVE:To investigate the utility of optical coherence tomography angiography (OCTA) for detecting pathologic vascularization within pigment epithelial detachments (PEDs). METHODS:This was a retrospective, cross-sectional, consecutive case series. Multimodal imaging (structural OCT, fluorescein, and indocyanine green angiography) was used as the gold standard to classify PEDs as nonvascularized or vascularized. Optical coherence tomography angiography imaging of the PED was subsequently and independently evaluated to classify PEDs as vascularized or nonvascularized. Specifically, OCTA images were evaluated for the presence of abnormal flow on cross-sectional OCTA and the presence of a vascular complex on en face OCTA. Comparisons between OCTA and the gold standard were determined. RESULTS:Sixty-four eyes of 49 patients were evaluated. A total of 18 eyes were classified as nonvascularized PED, and 46 eyes were classified as vascularized PED using the gold standard. Optical coherence tomography angiography was found to have a sensitivity of 76%, specificity of 61%, positive predictive value of 83%, and negative predictive value of 50% for detecting vascularized PEDs. False positive cases in the nonvascularized PED group were due to projection or flow artifacts from hyperreflective material overlying the PED. False negative cases were seen in eyes with minimal exudation on structural OCT and also those manifesting retinal pigment epithelial tears. CONCLUSION/CONCLUSIONS:Our proposed two-step approach of OCTA interpretation, first using cross-sectional OCTA and then en face OCTA, may allow the detection of vascularization within PEDs and, in some cases, reduce the need for conventional angiography. Increased awareness about potential artifacts and limitations of OCTA may help clinicians interpret OCTA more accurately.

PURPOSE: To describe the features of peripapillary pachychoroid syndrome (PPS), a novel pachychoroid disease spectrum (PDS) entity. METHODS: Medical records of 31 eyes (16 patients) with choroidal thickening associated with intraretinal and/or subretinal fluid in the nasal macula extending from the disk were reviewed (patients with PPS). Choroidal thickness was compared with 2 age-matched cohorts: typical PDS (17 eyes with central serous chorioretinopathy or pachychoroid neovasculopathy) and 19 normal eyes. RESULTS: The patients with PPS were 81% men aged 71 +/- 7 years. Peripapillary pachychoroid syndrome eyes displayed thicker nasal versus temporal macular choroids, unlike PDS eyes with thicker temporal macular choroids (P < 0.0001). Peripapillary intraretinal and/or subretinal fluid was often overlying dilated Haller layer vessels (pachyvessels). Fundus autofluorescence and fluorescein angiography illustrated peripapillary pigmentary mottling without focal leakage. Most PPS eyes (70%) exhibited other PDS findings including serous pigment epithelial detachment or gravitational tracks. Indocyanine green angiography illustrated dilated peripapillary pachyvessels and choroidal hyperpermeability. The disk was usually crowded, with edema noted in 4/31 (13%) eyes and mild late fluorescein disk leakage identified in half of the cases. Choroidal folds (77%), short axial lengths (39% less than 23 mm), and hyperopia (86%) were common. CONCLUSION: Peripapillary pachychoroid syndrome is a distinct PDS variant, in which peripapillary choroidal thickening is associated with nasal macular intraretinal and/or subretinal fluid and occasional disk edema. Recognition of PPS is important to distinguish it from disorders with overlapping features such as posterior uveitis and neuro-ophthalmologic conditions.

PURPOSE/OBJECTIVE:In an eye with macular atrophy due to age-related macular degeneration (AMD; complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA)), we correlated in vivo imaging to histology to characterize the atrophy border and evaluate the utility of optical coherence tomography (OCT) metrics suggested by previous histology. DESIGN/METHODS:Case study with clinicopathologic correlation. METHOD/METHODS:In vivo eye-tracked cross-sectional OCT scans at 13 and 8 months before death were compared to post-mortem histopathology. On OCT, the atrophy border was identified as either the descent of the external limiting membrane (ELM) towards Bruch's membrane (BrM) (representing gliosis), or the presence of choroidal hypertransmission (representing lack of shadowing by RPE). Thicknesses of RPE, basal laminar deposit (BLamD), and BrM was measured at 500 and 100 μm on the non-atrophic and atrophic sides of these borders, on in vivo eye-tracked OCT and histology matched to the same location. RESULTS:In all OCT scans, the ELM descent was visible. The RPE-BLamD band significantly thickened towards it (p<0.005), over time (p=0.015 and 0.043, at 500 and 100 μm, respectively). On OCT, the ELM descent delineated a smaller atrophic area than did hypertransmission. RPE-BLamD thicknesses manually measured on OCT overestimated histological thicknesses. BrM visibility varied with RPE status. CONCLUSION/CONCLUSIONS:Visible on OCT, the ELM descent is a histopathologic atrophy border supporting new terminology of cRORA, whereas hypertransmission reveals RPE degeneration. RPE-BLamD thickening across the macula, towards the atrophy and over time is confirmed. The presence of gliosis and thick RPE-BLamD suggests that macular atrophy is a late stage in disease progression, encouraging anatomical endpoints at earlier AMD stages, rather than atrophy enlargement.

Optical coherence tomography (OCT) images semi-transparent tissues noninvasively. Relying on backscatter and interferometry to calculate spatial relationships, OCT shares similarities with other pulse-echo modalities. There is considerable interest in using machine learning techniques for automated image classification, particularly among ophthalmologists who rely heavily on diagnostic OCT. Artificial neural networks (ANN) consist of interconnected nodes and can be employed as classifiers after training on large datasets. Conventionally, OCT scans are rendered as 2D or 3D human-readable images of which the smallest depth-resolved unit is the amplitude-scan reflectivity-function profile which is difficult for humans to interpret. We set out to determine whether amplitude-scan reflectivity-function profiles representing disease signatures could be distinguished and classified by a feed-forward ANN. Our classifier achieved high accuracies after training on only 24 eyes, with evidence of good generalization on unseen data. The repertoire of our classifier can now be expanded to include rare and unseen diseases and can be extended to other disciplines and industries.

PURPOSE/OBJECTIVE:To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases. DESIGN/METHODS:Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis. PARTICIPANTS/METHODS:Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4). METHODS:Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging. MAIN OUTCOME MEASURES/METHODS:Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging. RESULTS:Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9±37.8 μm and 65.4±27.9 μm, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns. CONCLUSIONS:Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging.

Purpose/UNASSIGNED:To determine if inner retinal layer reflectivity in eyes with acute central retinal vein occlusion (CRVO) correlates with visual acuity at 12 months. Methods/UNASSIGNED:Macular optical coherence tomography (OCT) scans were obtained from 22 eyes of 22 patients with acute CRVO. Optical intensity ratios (OIRs), defined as the mean OCT reflectivity of the inner retinal layers normalized to the mean reflectivity of the RPE, were measured from the presenting and 1-month OCT image by both manual measurements of grayscale B-scans and custom algorithmic measurement of raw OCT volume data. OIRs were assessed for association with final visual outcome. Cohort subgroup division for analysis was determined statistically. Results/UNASSIGNED:Eyes with poorer final visual acuity (≥20/70) at 1 year were more likely to have a higher ganglion cell layer OIR than eyes with better final visual acuity (<20/70) at 1 month (manually: 0.591 to 0.735, P = 0.006, algorithmically: 0.663 to 0.799, P = 0.014). At 1 month, eyes with a poorer final visual acuity demonstrated a higher variance of OIR measurements (algorithmically: 0.087 vs. 0.160, P = 0.002) per scan than eyes with better final visual acuity. Conclusions/UNASSIGNED:In acute CRVO, ganglion cell layer changes at 1 month, including increased reflectivity and increased heterogeneity of reflectivity signal as expressed as OIR and OIR variance, were associated with a poorer visual prognosis at 1 year. Technique calibration with larger sample sizes and automated integration into OCT platforms will be necessary to determine if OIR can be a clinically useful prognostic tool.

Objective/UNASSIGNED:To characterize features of extra-vascular optical coherence tomography angiography (OCTA) signals corresponding to hyperreflective intraretinal fluid across various exudative maculopathies. Design/UNASSIGNED:Multicenter, retrospective, observational study. Participants/UNASSIGNED:Eyes with various forms of exudative maculopathy including diabetic retinopathy (DR), retinal vein occlusion (RVO), and neovascular-age related macular degeneration (nvAMD). Methods/UNASSIGNED: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/UNASSIGNED:phantom. Results/UNASSIGNED: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/UNASSIGNED: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.

PURPOSE:To evaluate the size and location of macular atrophy in eyes with Type-1 neovascularization (NV) and age-related macular degeneration receiving chronic intravitreal anti-vascular endothelial growth factor therapy. METHODS:A retrospective review of a case series of 27 eyes with Type-1 NV and retinal pigment epithelial detachment (PED) having a minimum of 12 months follow-up was performed. Demographic information and visual acuity at baseline and the final follow-up were collected. Spectral-domain optical coherence tomography (OCT) and near-infrared reflectance were analyzed at 6-month intervals to detect and measure macular atrophy. Location and area (in square millimeter) of macular atrophy were measured using Heidelberg software tools. Also, OCT angiography was used to colocalize the area of Type-1 NV flow versus the location of atrophy. RESULTS:Twenty-seven eyes of 27 patients were included in this analysis. The median visual acuity was 20/50, mean age was 82.7 years, and mean number of injections was 29.5. A larger percentage of eyes (59.3%) developed atrophy predominantly eccentric to the PED versus predominantly overlying the PED (11.1%) when measured with spectral-domain OCT and near-infrared imaging. At the final follow-up, there was a larger area of atrophy surrounding the fibrovascular PED (mean, 3.326 mm) than overlying it (mean, 0.542 mm), and this was statistically significant (P = 0.0118). En-face OCT images were overlaid with OCT angiography in 11 eyes, and a predominantly eccentric pattern of atrophy was identified in 9 of 11 eyes. Using this method, the mean area of atrophy predominantly overlying the Type-1 NV was 1.652 mm (range of 0-10.464 mm), whereas the area of atrophy predominantly eccentric to the neovascular complex was 4.345 mm (range of 0.705-13.758 mm), and this was statistically significant (P = 0.0465). The average rate of atrophy progression was 1.04 mm/year (SD 0.938). CONCLUSION:With long-term anti-vascular endothelial growth factor therapy for eyes with Type-1 NV secondary to age-related macular degeneration, macular atrophy tends to develop predominantly eccentric to the PED and the neovascular flow imaged on OCT angiography. With chronic vascular endothelial growth factor suppression, Type-1 NV may evolve into a multilayered PED that may confer a protective effect to the overlying retinal pigment epithelium and outer retina.