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.

Background/aims Demonstrate that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to coexistent high-risk vascular diseases (HRVDs). Methods Cross-sectional study. Two hundred AMD subjects (aged 51-100 years; 121 women, 79 men) were recruited. Spectral domain optical coherence tomography, autofluorescence and near-infrared reflectance imaging, and lipid profiles were obtained. Subjects were assigned by health history questionnaires into those with or without HRVDs, defined as: cardiac valve defect (eg, aortic stenosis), myocardial defect (eg, myocardial infarction) and stroke/transient ischaemic attack. Masked readers assigned subjects into two groups: SDD (with or without drusen) and drusen (only). Univariate testing was performed by χ 2 test. We built multivariate regression models to test relationships of coexistent HRVD to SDD status, lipid levels and other covariates. Results The prevalence of HRVD was 41.2% (40/97) and 6.8% (7/103) in the SDD and non-SDD groups, respectively (correlation of SDD with HRVD, p=9×10 -9, OR 9.62, 95% CI 4.04 to 22.91). Multivariate regressions: only SDDs and high-density lipoprotein (HDL) in the first two HDL quartiles remained significant for HRVD (p=9.8×10 -5, 0.021, respectively). Multivariate regression model: SDDs and an HDL in Q1 or Q2 identified the presence of HRVD with the accuracy of 78.5%, 95% CI 72.2% to 84.0%. Conclusions High-risk cardiovascular and neurovascular diseases were accurately identified in an AMD cohort from SDDs and HDL levels. The SDDs may be related to inadequate ocular perfusion resulting from the systemic vasculopathies. Further research with this paradigm is warranted and might reduce mortality and morbidity from vascular disease.

PURPOSE/OBJECTIVE:To describe the multimodal imaging findings of extensive choroidal caverns within a choroidal nevus in an eye with pachychoroid spectrum disease. METHODS:A 69 year-old woman was referred with a known history of branch retinal vein occlusion (BRVO) in the right eye and choroidal nevus in the left eye. Fundus examination of both eyes (OU) revealed subretinal yellow deposits, suggestive of pachydrusen. Retinal venous collaterals were noted in the temporal macular of the right eye. A lightly pigmented choroidal lesion with nearly confluent overlying drusen and retinal pigment epithelial (RPE) alterations, consistent with chronic choroidal nevus, was noted in the macula of the left eye. RESULTS:Optical coherence tomography B-scans revealed thickened choroid (pachychoroid) with subfoveal choroidal thickness of 504 and 580 µm with large hyporeflective spaces suggestive of pachyvessels OU. In the region of the choroidal nevus, the choroidal vascular spaces appeared comparatively large and were classified as "caverns", measuring up to 480 µm in diameter. OCT angiography (OCTA) and indocyanine green angiography (ICGA) demonstrated absence of flow within the caverns. ICGA further illustrated choroidal vascular hyperpermeability with patchy hyperfluorescent areas OU. Widefield swept source OCT showed mild posterior scleral bowing, a feature occasionally documented with choroidal nevus, and highlighted greater hyporeflectivity and hypertransmission on OCT within the caverns compared to the non-cavernous choroidal vessels. CONCLUSION/CONCLUSIONS:Choroidal caverns can occur within choroidal nevus in the setting of pachychoroid disease.

The Henle fiber layer (HFL) is comprised of bundles of unmyelinated photoreceptor axons intermingled with outer Müller cell processes. The photoreceptor axons extend from the cell bodies located in the outer nuclear layer and radially project toward the outer plexiform layer, the inner third of which includes the synaptic junctional complexes and the outer two-thirds of which includes the HFL. The oblique path of the HFL provides unique structural and reflectance properties and this radial anatomy is highlighted in many macular disorders including those with macular star exudation and HFL hemorrhage. Recent investigations using multimodal imaging techniques, especially cross sectional and en face optical coherence tomography (OCT), have provided new perspectives regarding HFL disruption in retinal diseases. The aim of this review is to highlight the pathoanatomy and multimodal imaging, especially OCT, associated with HFL disruption that is present in various macular diseases. After describing the current knowledge of the embryology, anatomy, and physiology of the HFL, we review the existing imaging modalities that allow in vivo visualization of the HFL in the healthy and diseased retina. Finally, we report the clinical and imaging findings of acute HFL alteration in various macular disorders, including degenerative, inflammatory, and vascular conditions. Also, we propose a novel and signature OCT biomarker indicative of acute photoreceptor disruption involving the HFL, termed the "angular sign of HFL hyperreflectivity" (ASHH) of macular disease, to unify the pathoanatomy common to these various macular disorders and to provide clarity regarding the underlying pathogenesis.

PURPOSE/OBJECTIVE:To report a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) associated with primary Epstein-Barr virus (EBV) infection. METHODS:Multimodal imaging including color fundus photography, spectral domain optical coherence tomography (SD-OCT), blue light fundus autofluorescence (FAF), fluorescein angiography (FA) and indocyanine green angiography (ICGA). RESULTS:A 24-year-old otherwise healthy woman presented with an acute bilateral visual disturbance associated with cervical lymphadenopathy. SD-OCT showed bilateral foveal serous retinal detachment (SRD) with thickening of the ellipsoid zone (EZ) throughout the posterior pole corresponding to hyperautofluorescence on FAF, faint diffuse hyperfluorescence on FA without leakage, and mild late hyperfluorescence on ICGA. Systemic workup revealed an acute EBV infection. Within several weeks, multifocal SRDs developed in the macula and paramacula. The SRDs then became increasingly hyperautofluorescent with SD-OCT showing subretinal hyperreflective material. This vitelliform material then slowly resolved while the thickness of the surrounding EZ normalized. The FA and ICGA appeared normal at month 8. Visual acuity was 20/20 in both eyes at all times. No treatment was initiated. CONCLUSION/CONCLUSIONS:AEPVM may be associated with an acute EBV-infection. Acutely, multimodal imaging revealed findings consistent with RPE dysfunction and reduced photopigment density. Subsequent accumulation of vitelliform material gradually resolved over an 8 month follow up.

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.

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.

AIMS/OBJECTIVE:(1) To assess the morphology and 3-dimensional (3D) displacements of the eye globe and optic nerve (ON) in adduction/abduction using MRI. (2) To assess differences between healthy emmetropic and highly myopic (HM) subjects. METHODS:MRI volumes of both eyes from 18 controls and 20 HM subjects in primary gaze, abduction and adduction (15°) were postprocessed. All ONs were manually segmented and fitted to a 3D curve to assess ON tortuosity. ON displacements were evaluated in four quasicoronal planes which were perpendicular to the ON in primary gaze and were 3 mm apart. RESULTS:Axial length was higher in the HM group (28.62±2.60 vs 22.84±0.89 mm; p<0.0001). Adjusted ON tortuosities (ie, ON tortuosities estimated before myopia onset) were lower in HM eyes (0.9063±0.0591) versus controls (1.0152±0.02981) in primary gaze, adduction (0.9023±0.05538 vs 1.0137±0.0299) and abduction (0.9100±0.0594 vs 1.0182±0.0316); p<0.0001 for all cases. In all eyes, ON displacements in adduction were significantly different from those in abduction in the naso-temporal direction (p<0.0001 in all planes) but not in the supero-inferior direction. ON displacements in the posterior segments of the ON were smaller in the HM group in both gaze directions and were larger in the anterior-most ON segment in adduction only. CONCLUSION/CONCLUSIONS:The adjusted tortuosity of the ON was significantly lower in HM eyes, suggesting that eyes destined towards HM exhibited higher ON traction forces during eye movements before the onset of myopia. Our ON metrics may be valuable to explore a potential link between eye movements and axial elongation.

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.