Faculty Bibliography

PURPOSE/OBJECTIVE:To enable in vivo analysis of drusen composition and lifecycle, we assessed macular nodular and cuticular drusen using histology. METHODS:Median and interquartile range (IQR) of base widths of single (non-confluent) nodular drusen in 3 sources were determined histologically: 43 eyes of 43 clinically undocumented donors, in an online resource; one eye with punctate hyperfluorescence in fluorescein angiography (FA); and two eyes of one patient with bilateral "starry sky" cuticular drusen. All tissues were processed for high-resolution epoxy-resin histology and for cuticular drusen, transmission electron microscopy. RESULTS:All drusen localized between the retinal pigment epithelium basal lamina and inner collagenous layer of Bruch's membrane. They were solid, globular, homogeneously stained with toluidine blue, and uncovered by basal laminar deposit and basal mounds. Median base widths were 13.0 µm (Source 1, N=128 drusen, IQR 7.7, 20.0 µm), 15.3 µm (Source 2, N=87, IQR 10.6, 20.5 µm), and 7.3 µm (Source 3, N=78, IQR 3.9, 14.1 µm). CONCLUSIONS:In three samples, >90% of solitary nodular drusen were <30 µm, the visibility threshold in color fundus photography; these drusen are hyperfluorescent in FA. Whether these progress to soft drusen, known as high-risk from epidemiology studies and hypofluorescent, may be determinable from multimodal imaging datasets that include FA.

Purpose: To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient. Design: A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation). Participants: A White woman in her 90s treated with numerous intravitreal anti-VEGF injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). Methods: Clinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain OCT, OCT angiography, and fluorescein angiography. Eye tracking, applied to the 2 preserved donor eyes, enabled the correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy. Main Outcome Measures: Histologic/ultrastructural descriptions and diameters of vessels seen in clinical imaging. Results: Six vascular lesions were histologically confirmed (type 3 MNV, n = 3; deep retinal age-related microvascular anomalies [DRAMAs], n = 3). Pyramidal (n = 2) or tangled (n = 1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the subretinal pigment epithelium (RPE)"“basal laminar space or cross the Bruch membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and nonfenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. Deep retinal age-related microvascular anomaly lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMAs lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes. Conclusions: Type 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMAs are part of the type 3 MNV progression sequence. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

PURPOSE/OBJECTIVE:To describe the clinical and multimodal imaging features of stellate multiform amelanotic choroidopathy (SMACH; also known as serous maculopathy due to aspecific choroidopathy). METHODS:Retrospective observational case series of eyes presenting with SMACH. Multimodal imaging including fundus photography, optical coherence tomography (OCT), OCT-angiography (OCTA), and indocyanine green angiography (ICGA) was analyzed. RESULTS:Eighteen eyes from 18 patients (mean age: 28±19 years) were included. The mean follow-up duration was 9 years. Ophthalmoscopy showed a yellowish-orange, dendriform choroidal lesion. At presentation, subretinal fluid (SRF) was seen in 10/18 cases (56%). Eight patients (44%) showed no evidence of SRF during a mean follow-up of 6 years. Cross-sectional OCT showed hyperreflective fibrous-like changes within the inner choroid with choriocapillaris flow preservation on OCTA. En face OCT showed a hyperreflective choroidal lesion with finger-like projections oriented in a stellate configuration. On ICGA, SMACH showed early and late hypofluorescence. None of the cases showed lesion growth. CONCLUSIONS:SMACH appears to be a unilateral choroidopathy characterized by distinctive multimodal imaging features. As SRF was absent in some cases, while a dendriform pattern was a consistent finding in all eyes, we propose renaming this entity "stellate multiform amelanotic choroidopathy", a name which retains its prior abbreviation "SMACH".

BACKGROUND:To evaluate whether the status of vasculature at the top of type 1 macular neovascularisation (MNV) could function as mediator of the observed protective effect against the development of complete retinal pigment epithelial and outer retinal atrophy (cRORA). METHODS:In consecutive treatment-naïve patients, the vasculature at the anterior surface of the MNV was isolated using a slab designed to extract the most superficial vascular portion of the MNV lesion showing a choriocapillaris (CC)-like structure which we termed the 'neo-CC'. The ratio between the neo-CC area (isolated using this custom slab) and the MNV area (isolated using the standard outer retina-CC slab) at baseline and at last follow-up was evaluated. RESULTS:Forty-four eyes from 44 patients were included. 20 showed cRORA by the final follow-up (median 23 months), whereas 24 did not progress to atrophy (median 23.5 months). The proportion of MNV with neo-CC at the anterior surface was significantly lower in eyes which progressed to cRORA compared with those which did not. The multivariate regression showed that a lower proportion of neo-CC coverage over the MNV was associated with an increased odds for cRORA development. CONCLUSIONS:More extensive coverage of neo-CC is associated with a lower likelihood of development of macular atrophy in eyes receiving antivascular endothelial growth factor therapy, suggesting the protective effect of a type 1 MNV may be mediated by the development of a neo-CC and may provide insights into the biological significance of MNV as a response mechanism in eyes with age-related macular degeneration.

PURPOSE/UNASSIGNED:To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient. DESIGN/UNASSIGNED:A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation). PARTICIPANTS/UNASSIGNED:A White woman in her 90s treated with numerous intravitreal anti-VEGF injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). METHODS/UNASSIGNED:Clinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain OCT, OCT angiography, and fluorescein angiography. Eye tracking, applied to the 2 preserved donor eyes, enabled the correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy. MAIN OUTCOME MEASURES/UNASSIGNED:Histologic/ultrastructural descriptions and diameters of vessels seen in clinical imaging. RESULTS/UNASSIGNED:Six vascular lesions were histologically confirmed (type 3 MNV, n = 3; deep retinal age-related microvascular anomalies [DRAMAs], n = 3). Pyramidal (n = 2) or tangled (n = 1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the subretinal pigment epithelium (RPE)-basal laminar space or cross the Bruch membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and nonfenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. Deep retinal age-related microvascular anomaly lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMAs lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes. CONCLUSIONS/UNASSIGNED:Type 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMAs are part of the type 3 MNV progression sequence. FINANCIAL DISCLOSURES/UNASSIGNED:Proprietary or commercial disclosure may be found after the references.

PURPOSE/OBJECTIVE:To describe the clinical characteristics and multimodal imaging (MMI) features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with grey-yellow chorioretinal lesions surrounded by smaller satellite dots, a presentation referred to as "chrysanthemum lesions". METHODS:Retrospective, observational, multi-center case series of eyes with active iMFC and chrysanthemum lesions. Multimodal imaging features were reviewed and presented. RESULTS:Twenty-five eyes from 20 patients (12 women and 8 men), with a mean age of 35.8±17.0 years (range, 7 - 78 years) were included. Chrysanthemum lesions were equally located in the macula (48.0%) or the mid/far-periphery (52.0%). The number of lesions per eye varied from 1 (16.0%) to more than 20 (56.0%). On optical coherence tomography (OCT), chrysanthemum lesions showed typical features of iMFC, including subretinal hyperreflective material splitting the retinal pigment epithelium/Bruch's membrane (RPE/BrM). Chrysanthemum lesions were hypoautofluorescent on fundus autofluorescence imaging, hyperfluorescent on fluorescein angiography, hypofluorescent on indocyanine green angiography, and associated with choriocapillaris flow signal deficit on OCT-angiography. CONCLUSION/CONCLUSIONS:Active iMFC may present with findings resembling chrysanthemum lesions. The distinctive lesion morphology on ophthalmoscopic examination, the high number of lesions, and the high prevalence of exclusive mid- and far-peripheral involvement may represent a distinctive phenotype of iMFC.

PURPOSE/OBJECTIVE:To compare the imaging features of lesions showing hyporeflective posterior scleral excavation found near the insertions of the oblique extraocular muscles to the features and the natural course of Cogan scleral plaques. METHODS:Multimodal imaging with color fundus photography, spectral-domain optical coherence tomography (OCT), swept-source optical coherence tomography, and B-scan ultrasonography. RESULTS:A 71-year-old man and an 89-year-old man presented with ring-shaped hypopigmented lesions measuring between 200 μm and 300 μm transversally, and located along the superior vascular arcade and temporal to the fovea. All lesions were identified near the insertion of oblique muscles, with one observed in the temporal macula, and two found along the superotemporal arcades. Enhanced depth imaging-optical coherence tomography showed hyporeflective boat-shaped areas of scleral excavation with reduced choroidal thickness along their margins. B-scan ultrasonography showed the lesions to be intensely reflective with varying degrees of posterior shadowing. CONCLUSION/CONCLUSIONS:To our knowledge, this is the first report of excavated hyporeflective scleral lesions found near the oblique muscle insertions. Imaging and clinical data support the diagnosis of a posterior form of Cogan scleral plaque and are consistent with the natural course of this entity.

PURPOSE/OBJECTIVE:To investigate the association of nascent geographic atrophy (GA) preceding the development of exudative type 3 macular neovascularization (MNV) in patients with age-related macular degeneration (AMD). DESIGN/METHODS:Retrospective longitudinal study. PARTICIPANTS/METHODS:Patients with AMD diagnosed with treatment-naive exudative type 3 MNV in 1 or both eyes were evaluated. Inclusion criteria included serial tracked structural OCT examinations for ≥ 2 years before the detection of exudative type 3 MNV. METHODS:Clinical characteristics and retinal imaging, including structural OCT at baseline and at each follow-up examination, were analyzed. Eyes showing the presence of nascent GA during the follow-up were selected for analysis of prevalence, and clinical characteristics at the site of subsequent type 3 MNV development. MAIN OUTCOME MEASURES/METHODS:Description of the prevalence and clinical characteristics of nascent GA at the site of subsequent type 3 MNV development. RESULTS:Overall, 97 eyes affected by type 3 MNV meeting inclusion criteria were analyzed. Of 97 eyes (71 patients), 22 eyes of 21 patients (mean age 82 ± 9 years) showed nascent GA preceding exudative type 3 MNV. The observed prevalence of nascent GA preceding exudative type 3 MNV was 22.7% (95% confidence interval, 14.4%-31.0%). Exudative type 3 MNV developed a mean of 9 ± 6 months after detection of nascent GA. The presence of reticular pseudodrusen in the study eye did not significantly influence the timing of exudative type 3 MNV development after the observation of nascent GA (P > 0.1 in all analyses). Reduced best-corrected visual acuity was recorded at the exudative type 3 stage in comparison with the nascent GA stage (P = 0.003). CONCLUSIONS:As nascent GA may precede the development of exudative type 3 MNV, the detection of nascent GA in eyes with AMD may warrant closer surveillance to identify early exudative type 3 MNV warranting treatment. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found after the references.

PURPOSE/OBJECTIVE:Clinicopathologic correlation of two optical coherence tomography (OCT) features in neovascular age-related macular degeneration. METHODS:Case report, clinicopathologic correlation. RESULTS:A patient in her 90s was diagnosed with Type 3 macular neovascularization secondary to age-related macular degeneration in the index right eye and underwent intravitreal antivascular endothelial growth factor treatment for 5 years. A double-layer sign on in vivo OCT was correlated to calcified drusen on histology. Furthermore, hyperfluorescence on fluorescein angiography corresponded on histology to choroidal hypertransmission on OCT and retinal pigment epithelium atrophy above calcified drusen. CONCLUSION/CONCLUSIONS:A double-layer sign on OCT can represent nonneovascular subretinal pigment epithelium material including wide and flat calcific nodules. Furthermore, hyperfluorescence on FA, among different origins, can be due to a window defect corresponding to retinal pigment epithelium atrophy, which can be confirmed with OCT. Clinicopathological correlation using high-resolution histology can demonstrate the fine details available to clinical decision making through currently available in vivo OCT imaging.