Faculty Bibliography

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.

PURPOSE/OBJECTIVE:Macular perivenous retinal whitening results from hypoperfusion-induced ischemia of the middle retina that can occur in central retinal vein occlusion (CRVO). We describe an unusual case of recurrent CRVO with macular perivenous retinal whitening and retino-ciliary venous sparing in the setting of 2 prothrombotic diseases, antiphospholipid syndrome and Type II cryoglobulinemia. METHODS:A 50-year-old man presented with intermittent loss of vision in his right eye related to a recurrent CRVO. Color photography, optical coherence tomography, and fluorescein angiography were performed and compared with those obtained during a previous CRVO that occurred 6 years earlier in the same eye. RESULTS:On presentation, visual acuity was hand motion in the right eye, 20/30 in the left eye. Funduscopic examination of the right eye showed vascular tortuosity, scattered retinal hemorrhages, and retinal whitening in the macula. Optical coherence tomography showed hyperreflectivity of the middle layers of the retina that correlated with the areas of retinal whitening. A discrete area of retinal sparing was noted in the superonasal macula that, on fluorescein angiography, corresponded to the distribution of a single retino-ciliary vein. A review of retinal imaging obtained during the patient's previous CRVO showed similar but more subtle findings of retino-ciliary sparing. Laboratory testing revealed antiphospholipid syndrome and Type II cryoglobulinemia. As the patient's CRVO progressed and subsequently stabilized after treatment in the following months, this area of venous sparing remained the only functional, nonischemic retinal tissue in his macula. Presumably, this vein possessed privileged and uncompromised blood flow by circumventing the occluded venous circulation. CONCLUSION/CONCLUSIONS:Macular perivenous retinal whitening should be considered in the differential diagnosis of retinal whitening and occurs in CRVO secondary to hypoperfusion-induced middle retinal ischemia. To our knowledge, this case represents the first description of retino-ciliary venous sparing of the retina in CRVO.

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.

PURPOSE/OBJECTIVE:To analyze the changes in visual acuity and subfoveal choroidal thickness in patients with non-neovascular age-related macular degeneration (AMD) and drusenoid pigment epithelium detachments (PED). DESIGN/METHODS:Consecutive observational case series. METHODS:Observational retrospective review of eyes diagnosed with drusenoid PED in a single clinical setting. Demographic and clinical data included age, gender, laterality, best corrected visual acuity (BCVA) and subfoveal choroidal thickness measured at baseline, before and after the collapse of the PED, and at the last available follow-up. The presence of geographic atrophy (GA) was also assessed. RESULTS:Thirty-seven eyes of 25 patients (18 females) were included in the analysis. Mean age at baseline was 71 ± 8.4 years. During a mean follow-up period of 4.9 ±1.9 years, PED collapse was observed in 25 eyes (68%). Mean BCVA, mean maximum PED height and mean subfoveal choroidal thickness significantly decreased from baseline to the last available follow-up (p<0.001) in patients showing PED collapse. Choroidal thinning was faster during the PED collapse (speed rate of 35.9 microns/year). From those, 23 eyes (92%) developed GA. A significant correlation between the area of GA and the decrease in choroidal thickness was found (p=0.010). CONCLUSIONS:Choroidal thickness significantly decreased in eyes showing drusenoid PED collapse, but not in eyes in which the PED persisted. A significant correlation with resultant GA area following PED collapse and the magnitude of choroidal thinning was found. Further studies are warranted to better understand the mechanisms involved in the occurrence of choroidal changes during the lifecycle of drusenoid PEDs.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

PURPOSE/OBJECTIVE:Mutations in the eyes shut homolog (EYS) gene are a frequent cause of autosomal recessive retinitis pigmentosa (arRP). This study used multi-modal retinal imaging to elucidate genotype-phenotype relationships in EYS-related RP (EYS-RP). DESIGN/METHODS:Cross-sectional study. METHOD/METHODS:Multimodal retinal imaging and electrophysiologic testing was assessed for 16 patients with genetic confirmation of EYS-RP. RESULTS:A total of 27 unique EYS variants were identified in 16 patients. Seven patients presented with an unusual crescent-shaped hyperautofluorescent (hyperAF) ring on fundus autofluorescence (FAF) imaging encompassing a large nasal-superior area of the posterior pole. Three patients had a typical circular or oval perifoveal hyperAF ring and six patients had no hyperAF ring. Spectral domain optical coherence tomography (SD-OCT) and en face OCT showed preserved ellipsoid zone and retinal thickness spatially corresponding to areas within the hyperAF rings. Eleven patients presented with a rod-cone dystrophy on full-field electroretinogram (ffERG), one patient presented with cone-rod dystrophy, and four patients did not undergo ERG testing. A significant spatial association was found between EYS variant position and autofluorescent phenotype, with variants occurring at a nucleotide position greater than GRch37 6:65300137 (c.5617C) being more associated with patients exhibiting autofluorescent rings at presentation. CONCLUSIONS:EYS-RP is a heterogeneous manifestation. Variants occurring in positions closer to the C-terminus of EYS are more common in patients presenting with autofluorescent rings on FAF imaging.

PURPOSE: To compare the prevailing patterns of Haller vessel arrangements at the posterior pole between healthy eyes and those with central serous chorioretinopathy (CSC) using en face optical coherence tomography. METHODS: Eyes of normal subjects and patients with acute or chronic CSC underwent optical coherence tomography imaging (RTVue 100; Optovue Inc, Fremont, CA). En face sections at the level of the Haller layer were classified by two masked graders into five mutually exclusive morphologic categories (temporal herringbone, branched from below, laterally diagonal, double arcuate, and reticular). The relative prevalence of each Haller vessel arrangement pattern was determined for each phenotype. RESULTS: Numbers of eyes examined were as follows: 154 eyes of 77 normal subjects; 41 eyes of 31 patients with acute CSC; and 39 eyes of 33 patients with chronic CSC. The mean age of participants was 44.4 +/- 14.6 years for healthy subjects (M:F = 37:40), 48.5 +/- 8.2 years (M:F = 24:7) for acute CSC, and 65.3 +/- 13.1 years (M:F = 28:5) for chronic CSC. The relative prevalence of each Haller vessel arrangement pattern differed by phenotype. The temporal herringbone pattern was most prevalent in healthy eyes (49.2%), whereas a reticular pattern was most prevalent in eyes with acute and/or chronic CSC (combined, 48.8%). CONCLUSION: A significant difference was observed in the prevalence of respective Haller vessel arrangement patterns between eyes of normal subjects and those of patients with either acute or chronic CSC. Although further study is needed to determine the mechanistic factors underlying these differences, and the hemodynamic implications, our data suggest that en face optical coherence tomography may find a formal role in choroidal disease classification.

PURPOSE/OBJECTIVE:To describe a novel imaging technique, we call "dense B-scan optical coherence tomography angiography" (DB OCTA) in which thin dense raster scans are used to produce highly resolved structural B-scans with superimposed flow signal that provide precise correlation between retinal microstructure and blood flow. DESIGN/METHODS:Observational case series METHODS: Normal eyes and eyes with macular findings of interest were imaged with DB OCTA in which 150-400 OCT B-scans were acquired within a narrow area (from a single line to 1°) with a width of 10 to 30°. B-scans containing 5-7 consecutive frames were processed for OCTA signal and then combined and visualized post-acquisition by application of a Gaussian filter across neighboring scans. The result was a single, smoothed, high resolution image that contained both structural and flow information. Tracked follow-up DB OCTA was used to detect subtle changes in pathology over time. RESULTS:Two hundred and thirty-seven eyes from 205 subjects aged 18-100 years (mean 72.88 ± 14.74) with a diverse range of macular findings were imaged with DB OCTA. Highly resolved scans showing precise localization of flow signal were readily obtained, even in patients with poor visual acuity and/or poor fixation. We present clinical examples that demonstrate the utility of DB OCTA for visualizing the associations between retinal microstructure and blood flow. CONCLUSIONS:DB OCTA enables precise correlation between retinal microstructure and blood flow. The ability to obtain accurately aligned follow-up DB OCTA studies has the potential to refine the understanding and clinical management of a wide range of macular diseases.