Faculty Bibliography

Purpose/UNASSIGNED:Basal laminar deposit (BLamD) is a consistent finding in age-related macular degeneration (AMD). We quantified BLamD thickness, appearance, and topography in eyes of aged donors with and without AMD and evaluated its relationship to other components of the retinal pigment epithelium-basal lamina/Bruch's membrane (RPE-BL-BrM) complex. Methods/UNASSIGNED:Donor eyes (n = 132) were classified as normal (n = 54), early to intermediate AMD (n = 24), geographic atrophy (GA; n = 13), and neovascular AMD (NV; n = 41). In high-resolution histology, we assessed RPE, BLamD, and BrM thicknesses and phenotypes at 3309 predefined locations in the central (foveal and perifovea) and superior (perifoveal) sections. Pre-mortem optical coherence tomography (OCT) imaging of a 90-year-old woman was compared to postmortem histopathology. Results/UNASSIGNED:In non-atrophic areas of AMD eyes, the RPE-BLamD is thick (normal = 13.7 µm, early-intermediate = 16.8 µm, GA = 17.4 µm, NV = 18.7 µm), because the BLamD is thick (normal = 0.3 µm, early-intermediate = 5.5 µm, GA = 4.1 µm, NV = 5.3 µm). RPE layer thickness is similar across these stages. Disease-associated variants of BLamD (thick, late, basal mounds) cluster subfoveally. A thick BLamD is visible on OCT as a hyporeflective split in the RPE-BL-BrM complex. BrM is thin (3.5 µm) in NV (normal = 4.2 µm, early to intermediate = 4.4 µm, and GA = 4.2 µm). Conclusions/UNASSIGNED:The RPE-BL-BrM complex is thick in AMD, driven by the accumulation and expansion of BLamD rather than expansion of either three-layer BrM, RPE-BL, or RPE. BLamD is clinically appreciable by OCT in some patients as a non-neovascular "split RPE-BL-BrM complex" or "double-layer sign." BLamD may contribute toward the formation and progression of high-risk drusen yet also exhibit protective properties.

PURPOSE/OBJECTIVE:To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN/METHODS:Multicenter retrospective observational case series. PARTICIPANTS/METHODS:Sixty-three patients with SIC in 1 eye. METHODS:Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES/METHODS:Standardized grading of imaging features. RESULTS:Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 μm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS:In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

PURPOSE/OBJECTIVE:To evaluate the features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6mg/0.05ml for treatment of neovascular age-related macular degeneration (AMD). DESIGN/METHODS:Retrospective case series. PARTICIPANTS/METHODS:Fifteen eyes from 12 patients identified from 10 centers in the United States. METHODS:Review of patient demographics, ophthalmologic examination and retinal imaging. MAIN OUTCOME MEASURES/METHODS:Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography and treatment strategies RESULTS: The number of previous anti-VEGF IVIs ranged between 2 to 80 in the affected eye prior to the switch to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days following brolucizumab IVI. Mean visual acuity prior to brolucizumab IVI was logMAR 0.426 (Snellen equivalent 20/53) and at diagnosis of retinal vasculitis was logMAR 0.981 (Snellen equivalent 20/191, range 20/25 to 20/1600) (P= 0.008). All affected eyes showed intraocular inflammation with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular non-perfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular non-perfusion and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients and 3 patients had negative evaluation for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, topical) and two eyes had vitrectomy without improvement in vision. After mean follow-up of 25 days, mean visual acuity was logMAR 0.833 (Snellen equivalent 20/136), which was reduced compared to baseline (P=.033). CONCLUSIONS:Retinal vasculitis and IOI after brolucizumab IVI is characterized by variable occlusion of large and /or small retinal arteries and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required as vitreous cells may obscure visualization of retinal details.

PURPOSE/OBJECTIVE:To describe the presence of subretinal lipid globules (SLG), analyze the multimodal imaging features inherent in their optical properties and provide a means to distinguish them from other retinal structures and clinical signs. DESIGN/METHODS:Retrospective cohort study. METHODS:The clinical data and multimodal imaging features of 39 patients (49 eyes) showing SLG were evaluated. Patients underwent color fundus photography, near-infrared reflectance (NIR), spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) and OCT angiography. In vitro phantom models were used to model OCT optical properties of water, mineral oil, and intralipid droplets and to investigate the optical mechanisms producing hypertransmission tails beneath SLG. RESULTS:The SLG were not visible in color fundus photographs or NIR images. With both SD- and SS-OCT B-scans, SLG appeared as 31-157 micron round hyporeflective structures demonstrating a characteristic hypertransmission tail previously described with lipid globules found in the choroid and in neovascular membranes. Similarly, with en face OCT, SLG appeared as small round hyporeflective structures. SLG were encountered most often in eyes with neovascular age-related macular degeneration (AMD) that had type 1 macular neovascularization (MNV) (91.8%). Of these eyes, 93.3% were receiving intravitreal anti-vascular endothelial growth factor (VEGF) therapy (median of 15 injections) with a mean follow-up of 52.6 months. The number of prior injections positively correlated with the number of SLG. The detection of MNV preceded the presence of SLG in 66.7% of cases. En face OCT showed that in many eyes (49%) SLG appeared in clusters of >10. In 38.8% of eyes, SLG were found overlying type 1 MNV and in 44.9% of eyes, often those with more numerous SLG, the SLG were located near the lesion border. In 2 eyes with AMD followed for nonexudative type 1 MNV, SLG were detected prior to the detection of other imaging signs of exudation. SLG were observed in several other exudative macular diseases. Phantom models demonstrated that the hypertransmission tail beneath SLG is related to a lensing effect produced by these hyporeflective spherical structures. CONCLUSIONS:SLG are a newly recognized OCT feature frequently seen in eyes receiving intravitreal anti-VEGF therapy for type 1 MNV due to AMD. OCT B-scans show SLG as small, round, hyporeflective structures with a characteristic hypertransmission tail. This OCT signature is influenced by the OCT focal plane and it relates to reduced signal attenuation through oil and a lensing effect created by a higher refractive index compared to surrounding tissue.

PURPOSE/OBJECTIVE:To study the early anatomic choroidal alterations in eyes with chronic central serous chorioretinopathy (CSCR) undergoing photodynamic therapy (PDT). DESIGN/METHODS:Multicenter retrospective cohort study. METHODS:A total of 77 patients and 81 eyes with chronic CSCR treated with PDT and 64 untreated fellow eyes were evaluated. Central macular thickness (CMT) and choroidal features including subfoveal choroidal thickness (SFCT), total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were analyzed. Choroidal vascularity index (CVI) was calculated in all study eyes at baseline and at 1- and 3-months post-PDT. RESULTS:at the 1-month follow-up visit, respectively (P = .01). No significant changes were recorded for SCA and CVI. In the fellow eye group, VA, CMT, and all choroidal parameters showed no differences between baseline and any follow-up visits (all P > .05). CONCLUSIONS:After PDT for chronic CSCR we observed sustained reductions in CMT and SFCT, while reductions in TCA and LCA were only noted at the 1-month follow-up interval. These choroidal parameters may provide additional quantitative biomarkers to evaluate the anatomic response to therapy but await further prospective validation.

Purpose/UNASSIGNED:To use structural criteria to reconcile the three-dimensional organization and connectivity of the parafoveal microvasculature. Methods/UNASSIGNED:The parafoveal microvasculature was perfused and labeled in 16 normal human donor eyes for lectin, alpha smooth muscle actin, and filamentous actin. Established structural criteria gathered using confocal microscopy, including vessel diameter, endothelial cell morphology, and presence/density of smooth muscle cells, were used to differentiate arteries, arterioles, capillaries, venules, and veins. Three-dimensional visualization strategies were used to define the connections between retinal arteries and veins within the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Results/UNASSIGNED:The parafoveal microvasculature has two different inflow patterns and seven different outflow patterns. The SVP and ICP were connected to retinal arteries by arterioles. Inflow into the DCP occurred only via small arterioles (a1; mean diameter, 8.3 µm) that originated from the ICP. Direct connections between the DCP and retinal arteries were not identified. Each capillary plexus formed its own venule that drained independently or in conjunction with venules from other plexuses into a retinal vein at the level of the ganglion cell layer. For the DCP, a1 was significantly smaller than its draining venule (mean diameter, 18.8 µm; P < 0.001). Conclusions/UNASSIGNED:The SVP and ICP of the parafoveal microvasculature have both in series and in parallel arterial and venous connections. Arterial supply to the DCP originates from the ICP, but with direct drainage to the retinal vein. These findings may help to develop an understanding of the pattern of retinal lesions characterizing a myriad of retinal vascular diseases.

PURPOSE/OBJECTIVE:To describe the clinical and multimodal imaging findings of a series of cases of serous macular detachment (SMD) caused by Best disease (BD) masquerading as neovascular age-related macular degeneration or central serous chorioretinopathy that were inappropriately treated with intravitreal anti-vascular endothelial growth factor or laser therapy. This study will also present data to support age-related progressive choroidal thickening in BD patients, which may play a role in the development of SMD in this population. METHODS:Clinical examination and multimodal imaging findings, including color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and optical coherence tomography-angiography, were reviewed and analyzed. Subfoveal choroidal thickness was also formally measured, and an age-related choroidal thickness analysis was performed and compared with a normal population. RESULTS:Twenty-six eyes of 13 patients (5 women) were included. Median age was 44 years. Nine patients presented with a history of SMD and subretinal fluid recalcitrant to various therapies, including intravitreal anti-vascular endothelial growth factor injections and photodynamic therapy. Best disease was subsequently diagnosed genetically in six patients and by detailed family history in seven. Mean logarithm of the minimum angle of resolution best-corrected visual acuity for all 26 eyes at last follow-up was +0.36 (Snellen equivalent of 20/46). Subfoveal choroidal thickness positively correlated with age for our cohort, increasing linearly at a rate of 25.6 µm per decade (R = 0.64; P < 0.001). Choroidal neovascularization was identified in four eyes on optical coherence tomography angiography, but these eyes did not respond to anti-vascular endothelial growth factor treatment. CONCLUSION/CONCLUSIONS:The diagnosis of BD should be considered in patients presenting with SMD and recalcitrant subretinal fluid masquerading as neovascular age-related macular degeneration or chronic central serous chorioretinopathy to avoid unnecessary treatment procedures. The positive correlation of subfoveal choroidal thickness with age in BD patients may be a factor in the pathogenesis and development of SMD in this population. Recognizing the multimodal imaging features of SMD associated with BD, described in detail in this study, will guide practitioners to the accurate diagnosis of BD and reduce the risk of unnecessary intraocular procedures with potential complications.

PURPOSE/OBJECTIVE:To identify common optical coherence tomography (OCT) characteristics of taxane-related CME (T-CME) to differentiate it from CME associated with other causes (O-CME) and to present multimodal imaging findings of T-CME. METHODS:To differentiate T-CME from O-CME, pooled SD-OCT images from 14 previous publications and images obtained from our multicenter case series of 3 patients with multimodal imaging of T-CME were compared with 16 consecutive cases of O-CME. Images were graded by 2 masked retinal specialists based on the presence of pre-specified OCT characteristics such as CME centered around fovea, outer retinal cysts more prominent compared with inner retinal cysts, continuous outer plexiform layer (OPL) and inner plexiform layer (IPL), intact outer retina layer, attenuation of outer retina layers by overlying retinal layers, and the presence of subretinal fluid. RESULTS:Comparing 19 and 16 SD-OCT images of T-CME and O-CME, respectively, T-CME showed a significantly higher rate of the continuous OPL and IPL layer and a higher composite score of the various pre-specified OCT features. All other individual features showed no significant difference between T-CME and O-CME. All our patients had T-CME that had vague petalloid patterns on the late-stage FFA, with late leakage on ICGA. OCT angiography in one case showed an intact foveal avascular zone. CONCLUSIONS:T-CME is a rare but important complication of taxane chemotherapy. Specific OCT features such as an intact continuous OPL and IPL layer combined with other OCT features can help distinguish T-CME from O-CME, and early diagnosis is clinically important as cessation of taxanes before the retinal layers are disrupted may prevent permanent vision loss.