Faculty Bibliography

PURPOSE/OBJECTIVE:To characterize and distinguish non-neovascular deep retinal age-related microvascular anomalies (DRAMA) from type 3 macular neovascularization (MNV) using volume rendering of optical coherence tomography (OCT) and OCT angiography (OCTA). DESIGN/METHODS:Retrospective, consecutive case series. SUBJECTS/METHODS:Consecutive patients with age-related macular degeneration (AMD) exhibiting de novo non-neovascular abnormalities within the deep vascular plexus (DCP) on high-resolution (High-Res) spectral domain and swept-source OCT/OCTA. Patients with retinal vascular alterations attributable to other disease entities were excluded. METHODS:Complete ophthalmologic examination and multimodal imaging including confocal fundus photography (CFP), spectral domain OCT (SD-OCT), High-Res SD-OCT and OCTA, and volume-averaged swept-source OCTA (SS-OCTA). Volume rendering of High-Res OCTA and averaged SS-OCTA were used to analyze capillary abnormalities and inflow/outflow connectivity pathways. MAIN OUTCOME MEASURES/METHODS:The primary outcomes were the characteristics of capillary abnormalities (number, size, shape, reflectivity, and location) and inflow/outflow connectivity pathways. Secondary outcomes were nearby changes in CFP and structural OCT (hyperreflective foci, outer retinal atrophy, and retinal pigment epithelium (RPE) atrophy). RESULTS:From 8 eyes of 8 patients, 2 DRAMA subtypes were identified: small diameter perifoveal capillary dilations with hyperreflective walls within the inner nuclear layer (type 1, n=4) and vascular outpouchings, typically multiple, extending posteriorly into Henle's fiber layer with reflectivity similar to adjacent normal retinal capillaries (type 2, n=10). Four eyes had both DRAMA subtypes. Three-dimensional visualization of OCTA data demonstrated DRAMA corresponding to dilations of DCP capillaries without direct inflow or outflow connections to the superficial plexus. Fundus photographs showed circular red dots in 3 eyes, all corresponding to type 1 DRAMA. DRAMA co-localized with hyperreflective foci in all cases. No lesions were found anterior to areas of retinal pigment epithelium or outer retina atrophy. Asymptomatic intraretinal exudation varied through a follow-up of up to 6 years, with no lesions progressing to type 3 MNV. CONCLUSIONS:In eyes with non-neovascular AMD, DRAMA includes two types of capillary dilations occurring without remodeling of the surrounding vascular network. DRAMA can resemble microvascular changes due to other causes and can masquerade as type 3 MNV. Mild intraretinal exudation can vary during follow up without progression to type 3 MNV.

PURPOSE/OBJECTIVE:To report a case of branch retinal artery occlusion associated with paracentral acute middle maculopathy on spectral-domain optical coherence tomography presumably related to heavy cannabis consumption. METHODS:Retrospective case report. Spectral-domain optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography were performed. RESULTS:A 21-year-old healthy man described the acute onset of superior visual field loss in his right eye. He admitted smoking approximately 15 g daily of cannabis for several weeks during COVID-19 confinement. Ophthalmoscopic examination of the right eye showed inferotemporal retinal whitening. Spectral-domain optical coherence tomography illustrated evidence of the ischemic cascade with diffuse hyperreflectivity of the inner and middle retinal layers within the central region of the retinal infarct and paracentral acute middle maculopathy at the border of the infarct. Optical coherence tomography angiography demonstrated predominant flow signal loss at the level of the deep retinal capillary plexus. Fluorescein angiography and complete systemic workup were unremarkable. CONCLUSION/CONCLUSIONS:Branch retinal artery occlusion and paracentral acute middle maculopathy may be related to heavy cannabis use as the result of transient arterial vasospasm.

Purpose:To characterize macular blood flow connectivity in vivo using high-resolution optical coherence tomography (HighRes OCT). Methods:Cross-sectional, observational study. Dense (6-µm interscan distance) perifoveal HighRes OCT raster scans were performed on healthy participants. To mitigate the limitations of projection-resolved OCT-angiography, flow and structural data were used to observe the vascular structures of the superficial vascular complex (SVC) and the deep vascular complex. Vascular segmentation and rendering were performed using Imaris 9.5 software. Inflow and outflow patterns were classified according to vascular diameter and branching order from superficial arteries and veins, respectively. Results:Eight eyes from eight participants were included in this analysis, from which 422 inflow and 459 outflow connections were characterized. Arteries had direct arteriolar connections to the SVC (78%) and to the intermediate capillary plexus (ICP, 22%). Deep capillary plexus (DCP) inflow derived from small-diameter vessels succeeding ICP arterioles. The most prevalent outflow pathways coursed through superficial draining venules (74%). DCP draining venules ordinarily merged with ICP draining venules and drained independently of superficial venules in 21% of cases. The morphology of DCP draining venules in structural HighRes OCT is distinct from other vessels crossing the inner nuclear layer and can be used to identify superficial veins. Conclusions:Vascular connectivity analysis supports a hybrid circuitry of blood flow within the human parafoveal macula. Translational Relevance:Characterization of parafoveal macular blood flow connectivity in vivo using a precise segmentation of HighRes OCT is consistent with ground-truth microscopy studies and shows a hybrid circuitry.

PURPOSE/OBJECTIVE:To present a clinicopathologic correlation of indolent, non-progressive multifocal choroidal lesions, clinically presumed to be lymphoid in nature, using multimodal imaging and histopathological analysis of a donor eye. DESIGN/METHODS:Case study and clinicopathologic correlation. PARTICIPANT/METHODS:A 77-year-old man of Caucasian ancestry was followed for nineteen years with indolent non-progressive multifocal choroidal infiltration of his right eye, presumed to be lymphocytic in nature based on the appearance of the lesions. METHODS:Multimodal imaging including fundus photography, B-scan ultrasonography, optical coherence tomography, fluorescein angiography, and indocyanine green angiography were performed throughout 19 years of follow up prior to the patient's death. The involved eye was preserved 21 hours postmortem and analyzed using standard histopathological and immunohistochemical techniques. MAIN OUTCOME MEASURES/METHODS:Correlation of findings on multimodal imaging with histopathological and immunohistochemical findings in the involved eye. RESULTS:Clinical examination over the course of 19 years showed no deterioration in visual acuity of the involved eye. Multimodal imaging revealed yellow-orange choroidal lesions that showed no appreciable progression during the 19 year follow up. These areas stained minimally on fluorescein angiography. Indocyanine green angiography revealed tortuous choroidal vessels and fluorescence blockage. Enhanced-depth imaging optical coherence tomography revealed hyporeflective homogenous choroidal thickening. Light microscopy, histopathology, and immunohistochemistry showed that the lesions were composed of small, mature-appearing B-cells that spared the choriocapillaris. The findings were most consistent with an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). CONCLUSIONS:Indolent non-progressive multifocal choroidal lymphoid lesions in this patient remained confined to the choroid on clinical examination and imaging for almost two decades, with no clinical evidence of extension into the retina. Light microscopy, histopathology, and immunohistochemistry postmortem showed that the lesions were composed of small, mature-appearing B-cells that spared the choriocapillaris. The findings were consistent with an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). This entity is distinct from more aggressive uveal and choroidal lymphoma and is expected to remain relatively stationary on long-term clinical follow-up, with a good visual prognosis.

PURPOSE/OBJECTIVE:To analyze the spectrum of the perivenular fern-like leakage on ultra-widefield fluorescein angiography (UWFA) and to discuss its potential implications in the current understanding of the retinal venous outflow. DESIGN/METHODS:Retrospective observational case series. PARTICIPANTS/METHODS:Eyes presenting with a fern-like pattern of dye leakage on UWFA were included in this study. METHODS:Analysis of the clinical characteristics and multimodal imaging findings using UWFA and wide-angle swept-source optical coherence tomography angiography (SS-OCTA). MAIN OUTCOME MEASURES/METHODS:To elucidate the disease spectrum, anatomic origin and clinical implications of this fern-like leakage. RESULTS:Multimodal retinal imaging from 40 eyes of 29 patients with fern-like leakage on UWFA was studied. Underlying etiologies included a wide range of inflammatory disorders including pars planitis (18 eyes), and central retinal vein occlusion (2 eyes). On UWFA, the fern-like leakage originated from the retinal capillaries and venules directly adjacent to the veins and spared the peri-arterial zone. This perivenular fern-like leakage involved the far periphery in all cases and progressed more diffusely and centripetally in cases with more severe intra-ocular inflammation. On wide-angle SS-OCTA, deep capillary plexus (DCP) flow signal impairment precisely co-localized with the perivenular fern-like leakage identified on UWFA. CONCLUSIONS:The fern-like leakage on UWFA refers to the distinctive perivenular dye leakage originating from the retinal capillaries and venules. Multimodal imaging correlation suggests predominant impairment at the level of the DCP. Axial symmetry of the fern-like leakage with the veins and sparing of the peri-arterial zone may support the dominant venous role of the DCP.

INTRODUCTION/UNASSIGNED:White dot syndromes are a heterogeneous group of diseases that affect different layers in the retina and choroid. Multimodal imaging is fundamental in the diagnosis, but also can be crucial in unveiling the pathogenesis of these entities. MATERIAL AND METHODS/UNASSIGNED:Literature review. RESULTS/UNASSIGNED:Optical coherence tomography (OCT) provides depth-resolved, histological grade images of the vitreous, retina, and choroid. This technology is very useful to localize the primary nature and level of pathology of the various white dot syndromes. En face OCT can provide additional information regarding the interrelationship of lesion types. Vascular involvement at the level of the retina, choriocapillaris or choroid can be assessed by en face OCT angiography (OCT-A) and is not limited by masking, leakage or staining as can occur with conventional angiography (fluorescein or indocyanine green angiography) which requires dye injection. CONCLUSION/UNASSIGNED:OCT and OCTA are fundamental in the diagnosis and follow-up of white dots syndromes.

Importance/UNASSIGNED:By validating optical coherence tomography angiography (OCTA) in the analysis of type 3 macular neovascularization secondary to age-related macular degeneration, the overall value of clinical OCTA for disease observation, diagnosis, and staging is increased. Objective/UNASSIGNED:To assess the association of in vivo OCTA of type 3 macular neovascularization secondary to age-related macular degeneration with corresponding ex vivo histology. Design, Setting, and Participants/UNASSIGNED:This study included clinical imaging, laboratory microscopy, and eye-tracked clinicopathologic correlation of a single case from a community-based practice evaluated at a university-based research laboratory from 2014 to 2019. Exposures/UNASSIGNED:Infrared reflectance and eye-tracked spectral-domain OCTA clinical imaging was correlated with ex vivo high-resolution histologic images of the preserved donor eye. Eye tracking, applied to the donor eye, enabled identification of histologic features corresponding with clinical OCTA signatures. Projection artifact removal based on 2-dimensional vessel-shape estimation and a Gaussian blur filter demonstrated a robust preservation of neovascular flow signal. Main Outcomes and Measures/UNASSIGNED:Histology findings associated with clinical OCTA signatures. Three-dimensional view of neovascularization via video. Results/UNASSIGNED:A White woman in her 90s with type 3 neovascularization secondary to age-related macular degeneration was treated with 37 intravitreal injections of ranibizumab and aflibercept in the right eye. The index lesion displayed a drusenoid pigment epithelium detachment, characteristic of type 3 neovascularization. OCTA decorrelation signal in the index lesion corresponded in histology to a collagen-ensheathed vascular complex contacting basal laminar deposit that outlasted the retinal pigment epithelium. The subretinal pigment epithelium-basal laminar space contained calcified material and glial processes. No connection between the choriocapillaris and this space was observed. Video showed a columnar tangle of flow signal in the outer nuclear layer, with inflow and outflow vessels connecting to the superficial artery and vein. Conclusions and Relevance/UNASSIGNED:While this study presents only 1 case in which a vascular connection between subretinal pigment epithelium-basal laminar space and choriocapillaris was undetected, these results support the potential value of OCTA for diagnosis. OCTA decorrelation signal of type 3 neovascularization corresponded with intraretinal neovessels on histology. Projection artifact removal based on 2-dimensional vessel-shape estimation and Gaussian blur filter demonstrated their potential value for further use in OCTA decorrelation signal processing.

INTRODUCTION/BACKGROUND:Since July 2021, a worldwide shortage of verteporfin (Visudyne®) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option. MATERIALS AND METHODS/METHODS:A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage. RESULTS:Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries. CONCLUSION/CONCLUSIONS:The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships.