Faculty Bibliography

PURPOSE/OBJECTIVE:Type 1 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) may sustain hypoxic and micronutrient-insufficient outer retinal cells compensatorily. We explored this hypothesis via histologic analysis of an eye with a shallow irregular retinal pigment epithelial elevation (SIRE) on OCT and good vision. DESIGN/METHODS:Case study and clinicopathologic correlation. PARTICIPANT/METHODS:A white woman with untreated nonexudative neovascular AMD and 20/30 visual acuity (left eye) and neovascular AMD (right eye), with 9 years' multimodal imaging before dying at 90 years of age. METHODS:The left eye was preserved 6.25 hours after death and prepared for submicrometer epoxy resin sections and transmission electron microscopy aligned to clinical OCT B-scans. Inside and outside the MNV area, layer thicknesses, phenotypes, and vascular density of native choriocapillaris and neovessels were measured. Lengths of choriocapillaries and intervening gaps in the index eye and in early AMD eyes and healthy eyes with similar age (n = 19 each) from the Project MACULA (Maculopathy Unveiled by Laminar Analysis) online histopathologic resource (http://projectmacula.cis.uab.edu/) were measured with custom software (Caps and Gaps). MAIN OUTCOME MEASURES/METHODS:Descriptive features, vascular density, histologic and OCT layer thicknesses, and distribution of choriocapillaries and intervening gaps. RESULTS:The SIRE correlated to a type 1 MNV that expanded slowly without evidence of exudation and with numerous choroidal vessels traversing Bruch's membrane defects, some visible on OCT. Tissue layers in and adjacent to the MNV area showed continuous RPE and characteristic AMD deposits. Capillary-like neovessels with fenestrations and caveolae resembling native choriocapillaris lined the retinal pigment epithelium (RPE) with a vascular density comparable with surrounding non-MNV areas. Relative to early AMD and healthy aged eyes, the index eye showed similar capillary lengths but larger gaps between vessels, indicating dropout. Outer nuclear layer thickness was preserved and showed less photoreceptor degeneration over areas of relative choriocapillaris health, including the type 1 MNV. CONCLUSIONS:Eyes with nonexudative type 1 MNV in AMD may progress to exudation, yet this stable MNV complex supported outer retinal structure for 9 years. Distinguishing features were numerous connecting vessels, high density of neovessels, continuous RPE, and slow growth. Maintaining beneficial type 1 MNV may be a therapeutic strategy.

Purpose/UNASSIGNED:To characterize macular blood flow connectivity using volume rendering of dense B-scan (DB) optical coherence tomography angiography (OCTA) data. Methods/UNASSIGNED:This was a prospective, cross-sectional, observational study. DB OCTA perifoveal scans were performed on healthy subjects using the Spectralis HRA+OCT2. A volumetric projection artifact removal algorithm and customized filters were applied to raw OCTA voxel data. Volume rendering was performed using a workflow on Imaris 9.5 software. Vascular graphs were obtained from angiographic data using the algorithm threshold-loops. Superficial arteries and veins were identified from color fundus photographs and connections between adjacent arteries and veins displayed using the shortest path algorithm. Connective pathway locations were analyzed with cross-sectional OCT and OCTA to determine their course through the superficial vascular complex (SVC) and the deep vascular complex (DVC). Results/UNASSIGNED:Fourteen eyes from seven subjects (mean age: 28 ± 5 years; 3 women) were included in this analysis. One hundred and twenty-six vascular connections were analyzed. In all cases, the shortest path connections between superficial arteries and veins coursed through the DVC. We did not identify shortest path connections confined to the SVC. Conclusions/UNASSIGNED:Volumetric analysis of vascular connectivity supports a predominantly in-series arrangement of blood flow between the SVC and DVC within the human perifoveal macula.

Purpose/UNASSIGNED:To evaluate the depth and pattern of retinal hemorrhage in acute central retinal vein occlusion (CRVO) and to correlate these with visual and anatomic outcomes. Methods/UNASSIGNED:Retinal hemorrhages were evaluated with color fundus photography and fluorescein angiography at baseline and follow-up. Snellen visual acuity (VA), central foveal thickness (CFT), extent of retinal ischemia, and development of neovascularization were analyzed. Results/UNASSIGNED:108 eyes from 108 patients were evaluated. Mean age was 63.6 ± 16.1 years with a predilection for the right eye (73.1%). Average follow-up was 17.2 ± 19.2 months. Mean VA at baseline was 20/126 and 20/80 at final follow-up. Baseline (P = 0.005) and final VA (P = 0.02) in eyes with perivascular nerve fiber layer (NFL) hemorrhages were significantly worse than in eyes with deep hemorrhages alone. Baseline CFT was greater in the group with perivascular hemorrhages (826 ± 394 µm) compared to the group with deep hemorrhages alone (455 ± 273 µm, P < 0.001). The 10 disc areas of retinal ischemia was more common in patients with perivascular (80.0%) and peripapillary (31.3%) versus deep hemorrhages alone (16.1%, P < 0.001). Neovascularization of the iris was more common, although this differrence was not significant, in the groups with peripapillary (14.3%) and perivascular (2.0%) NFL versus deep hemorrhages alone (0.0%). Conclusions/UNASSIGNED:NFL retinal hemorrhages at baseline correlate with more severe forms of CRVO, with greater macular edema, poorer visual outcomes, and greater risk of ischemia and neovascularization. This may be related to the organization of the retinal capillary plexus. The depth and pattern of distribution of retinal hemorrhages in CRVO may provide an easily identifiable early biomarker of CRVO prognosis.

PURPOSE/OBJECTIVE:To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. DESIGN/METHODS:Consensus meeting. PARTICIPANTS/METHODS:An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. METHODS:During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. MAIN OUTCOME MEASURES/METHODS:A consensus classification of neovascular AMD. RESULTS:The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. CONCLUSIONS:The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

PURPOSE/OBJECTIVE:To describe pre-exudative stage of exudative Perifoveal Vascular Anomalous Complex (ePVAC) referred to as non-exudative PVAC (nePVAC). DESIGN/METHODS:Retrospective non-comparative case series. METHODS:Patients diagnosed with nePVAC were identified at 4 retina referral centers worldwide. Multimodal retinal imaging including structural optical coherence tomography (OCT) and OCT-angiography (OCT-A) were performed at baseline and follow-up visits. RESULTS:Six eyes (6 patients, mean age 75±10years) were included. Unrelated chorioretinal diseases were diagnosed in the affected eyes in 5 of 6 cases. At the baseline, nePVAC is characterized by microvascular abnormalities featuring isolated, perifoveal, large intra-retinal aneurysm, surrounded by capillary rarefaction at OCT-A examination, without any sign of exudation with structural OCT, and without visual impairment. Four patients were followed for a mean of 21±14months. During the follow-up, 3 out of 4 eyes(75%) developed signs of exudation after a mean of 15±9months, associated with metamorphopsia and visual decline at the time of exudation. Best-corrected visual acuity(BCVA) decreased from 20/25 to 20/40 Snellen equivalent (p=0.035) and central macular thickness increased from 268±27 to 339±65μm (p=0.145). Three patients were treated with 2.3±0.6 intravitreal injections of anti-vascular endothelial growth factor without significant improvement of BCVA or macular edema. CONCLUSIONS:nePVAC may represent the sub-clinical pre-exudative stage of ePVAC, notable for an absence of exudation and/or visual impairment. nePVAC and ePVAC should be considered as part of the same spectrum, namely PVAC. Typically, nePVAC develops signs of exudation over time, causing metamorphopsia and visual decline and therefore these lesions warrant continued close monitoring with multimodal retinal imaging.

The use of laser to induce a retinal-choroidal anastomosis (RCA) through photomechanical and photothermal rupture of the retinal pigment epithelium/Bruch's membrane beneath a retinal vein has been performed in eyes with retinal vein occlusion to create an alternate pathway for retinal venous outflow. The authors document the multimodal imaging findings of a 64-year-old female with type 2 diabetes presenting with a parafoveal vascular lesion simulating type 3 macular neovascularization. A review of the medical history and the benign course of the lesion suggested its inadvertent origin from prior focal/grid laser to treat diabetic macular edema. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:244-248.].

Retinal vascular tortuosity may occur in a wide range of ocular disorders. When retinal vascular tortuosity involves both arteries and veins, and presents unilaterally and without hemorrhage, a diagnosis of Wyburn Mason syndrome (WMS) should be considered due to the potential morbidity and mortality associated with cerebral involvement. Magnetic resonance imaging (MRI) and MRI angiography (MRA) are important tools for identifying cerebral arteriovenous malformations (AVMs), but these imaging modalities have limited spatial resolution to detect very small vascular lesions. Annular array contact ocular ultrasound is a new imaging modality capable of detecting small intraorbital AVMs. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:239-243.].