Faculty Bibliography

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.

BACKGROUND/AIMS/OBJECTIVE:To analyse the long-term anatomic and visual outcomes of patients with peripapillary pachychoroid syndrome (PPS), a recently described entity in the pachychoroid disease spectrum. METHODS:This study retrospectively included patients from several retina centres worldwide. Visual acuity (VA), retinal thickness and choroidal thickness at baseline, 6 months and final follow-up were assessed. Temporal trends in VA and anatomic characteristics were evaluated. Visual and anatomic outcomes in eyes that were observed versus those that were treated were analysed. RESULTS:Fifty-six eyes of 35 patients were included with mean follow-up of 27±17 months. Median VA was 20/36 at baseline and remained stable through follow-up (p=0.77). Retinal thickness significantly decreased subfoveally (p=0.012), 1.5 mm nasal to the fovea (p=0.002) and 3.0 mm nasal to the fovea (p=0.0035) corresponding to areas of increased thickening at baseline. Choroidal thickness significantly decreased subfoveally (p=0.0030) and 1.5 mm nasal to the fovea (p=0.0030). Forty-three eyes were treated with modalities including antivascular endothelial growth factor injection, photodynamic therapy, and others. VA remained stable in treated eyes over follow-up (p=0.67). An isolated peripapillary fluid pocket in the outer nuclear layer was characteristic of PPS. CONCLUSION/CONCLUSIONS:Patients with PPS experienced decreased retinal oedema and decreased choroidal thickening throughout the course of disease. While some patients experienced visual decline, the overall visual outcome was relatively favourable and independent of trends in retinal or choroidal thickening.

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.

PURPOSE/OBJECTIVE:To describe the recovery timeline of spots and dots in multiple evanescent white dot syndrome. METHODS:Sequential multimodal retinal imaging including fundus autofluorescence and cross-sectional and en face optical coherence tomography was performed to track the development and resolution of spots and dots in a case of multiple evanescent white dot syndrome. RESULTS:En face optical coherence tomography showed that the spots are the result of ellipsoid zone loss and are hyperautofluorescent due to unmasking of the underlying retinal pigment epithelium autofluorescence. Conversely, the dots are hyperreflective with cross-sectional and en face optical coherence tomography and hyperautofluorescent, which we propose may be due to accumulation of degenerated photoreceptor material including fluorophores with autofluorescent capability such as precursors of A2E. The earlier resolution of the hyperautofluorescent spots allowed for later detection of the hyperautofluorescent dots. CONCLUSION/CONCLUSIONS:This case report illustrates the different recovery timelines of spots and dots in multiple evanescent white dot syndrome. Although both lesion types are hyperautofluorescent, the mechanism of autofluorescence is distinctive and may be explained by their contrasting pathoanatomy.

PURPOSE/OBJECTIVE:To report new multimodal imaging features that enhance our understanding of the inflammatory and ischemic nature of acute idiopathic maculopathy (AIM) and to correlate structural and functional changes due to a reversible initial choroidal ischemia over a clinical course of 3.5 months. METHODS:A 31-year-old man presented with acute central vision loss in his right eye due to coxsackievirus-associated AIM. Serial multimodal retinal imaging including confocal true color fundus photography, blue-light fundus autofluorescence (BAF), near-infrared reflectance (NIR), spectral domain optical coherence tomography and swept-source optical coherence tomography (SD-OCT + SS-OCT), and en face SS-OCT angiography (SS-OCTA) were performed over a 3.5-month follow-up. Eidon true color confocal scanner camera (Centervue, Padova, Italy) was used for color and BAF imaging. Near-infrared reflectance and SD-OCT images were obtained with the Heidelberg Spectralis OCT (HRA2 + OCT; Heidelberg Engineering, Heidelberg, Germany). For SS-OCT and en face SS-OCT and SS-OCTA images, the PLEX Elite 9,000 (Carl Zeiss Meditec, Inc, Dublin, CA) was used. Central alterations in choriocapillaris flow were analyzed with SS-OCTA using the University of Washington choriocapillaris (CC) flow deficit quantification algorithm available through the ARI Network. Flow deficit area and density values were analyzed and compared between the first and last examinations. Corresponding en face OCT imaging was used to distinguish true flow defects from artifacts secondary to shadowing. RESULTS:In the acute stage of AIM, a bacillary layer detachment appearing as a yellow-grayish foveal elevation surrounded by a hypopigmented parafoveal ring was evident in a Bull's eye configuration, corresponding to a hyperreflective ring upon NIR and a hyperautofluorescent ring with BAF. SD + SS-OCT showed mostly intraretinal fluid consistent with a bacillary layer detachment in conjunction with a thickened inner choroid. At presentation, SS-OCTA demonstrated a marked reduction of choriocapillaris flow signal. At 1 week, early resolution of retinal fluid was followed by restoration of the ellipsoid zone at 5 weeks, while restoration of the interdigitation zone and reduction in retinal pigment epithelium/Bruch membrane complex thickening occurred more slowly. Swept-source OCT angiography showed a gradual, but incomplete, recovery of inner choroidal flow signal at 3.5-month follow-up. CONCLUSION/CONCLUSIONS:Acutely, AIM may present with a photoreceptor splitting foveal bacillary layer detachment associated with a marked reduction in inner choroidal flow signal on SS-OCTA. Thereafter, restoration of the outer retinal layers and gradual normalization of choroidal flow signal appear to support the often-benign nature of the disease.

PURPOSE/OBJECTIVE:To describe clinical features including multimodal imaging in a rare case of presumed embolic cilioretinal artery occlusion with long-term follow-up examination. METHODS:A 61-year-old man presented after noticing an acute-onset central scotoma in the left eye during coronary arteriography. Fundus color photography, red-free imaging, near-infrared reflectance, spectral domain optical coherence tomography (OCT), fluorescein angiography, and swept-source OCT angiography were performed. RESULTS:Color and red-free fundus imaging both showed retinal whitening in the territory corresponding to a cilioretinal artery in the left eye. Consistent with an ischemic event, the near-infrared reflectance showed a hyporeflective area in the same location. Spectral domain OCT showed hyperreflectivity and generalized thickening of the inner nuclear layer, ganglion cell layer, and retinal nerve fiber layer. Seven years later, color, red-free, and near-infrared reflectance imaging appeared normal, but the spectral domain OCT showed thinning of all retinal layers in the affected area. Furthermore, swept-source OCT angiography demonstrated markedly reduced capillary flow signal in the superficial and deep capillary plexuses, corresponding to a persistent scotoma described by the patient. CONCLUSION/CONCLUSIONS:This case report illustrates hallmark features of a rare presumed embolic cilioretinal artery occlusion and its long-term manifestations with thorough historical and multimodal imaging data. When standard fundus imaging with color, red-free, and near-infrared reflectance appears normal years after a retinal vascular insult, OCT and OCT angiography can corroborate a patient's persistent visual deficit and provide clarity to the diagnosis.

PURPOSE/OBJECTIVE:To report the clinical presentation and imaging features in a case of bilateral self-inflicted handheld laser-induced maculopathy which masqueraded as progressive posterior uveitis in a patient with suspected IgG4-related disease. METHODS:Case report with clinical history, fundus photographs, fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography. RESULTS:A young Asian Indian man presented with sudden progressive bilateral visual loss over the past 1 week. He was being treated with oral corticosteroids for multiple subcutaneous skin lesions believed to be due to IgG4-related disease. Findings included bilateral central areas of outer retinal disruption with eccentric linear and serpentine lesions showing hypoautofluorescence. Hyperreflective bands extending from the retinal pigment epithelium and interdigitation zone to the outer plexiform layer were present on swept-source optical coherence tomography. After careful history and evaluation of multimodal imaging, posterior uveitis was excluded, and a diagnosis of handheld laser-induced maculopathy was established. CONCLUSION/CONCLUSIONS:Pattern recognition is important in establishing a diagnosis of self-inflicted handheld laser-induced maculopathy which can masquerade as posterior uveitis. Increasing availability of powerful Class IIIb laser devices in both developed and developing countries will likely increase the incidence of this entity.

PURPOSE/OBJECTIVE:To report a very late recurrence of choroidal neovascularization (CNV) in elderly patients with noninfectious multifocal choroiditis (MFC). METHODS:Retrospective case series of patients with MFC with confirmed recurrence of CNV. Choroidal neovascularization was diagnosed with multimodal imaging, including optical coherence tomography angiography. Multifocal choroiditis-associated CNV eyes were treated with intravitreal injections of anti-vascular endothelial growth factor medication. RESULTS:Four eyes of three patients were included in our study, with a mean (range) age of 73 years (67-78). The period between the original CNV and the recurrence was 53 years, with a range of 48-60 years. The mean number (range) of injections given after the late recurrence per eye was 7 (5-11). The mean duration (range) of follow-up post-treatment initiation was 93 (40-122) weeks. All eyes improved to 20/30 visual acuity or better at 6 months after initial treatment. CONCLUSION/CONCLUSIONS:Patients with MFC are never exempt from recurrent CNV, warranting follow-up in perpetuity. Age-related factors are important to consider which may increase the susceptibility for activating MFC-associated CNV in elderly people. Macular neovascularization could respond to a standard approach to management, in these patients with MFC, by a judicious use of intravitreal injections of anti-vascular endothelial growth factor therapy.

PURPOSE/OBJECTIVE:Melanotic cells with large spherical melanosomes, thought to originate from retinal pigment epithelium (RPE), are found in eyes with neovascular age-related macular degeneration (nvAMD). To generate hypotheses about RPE participation in fibrosis, we correlate histology to clinical imaging in an eye with prominent black pigment in fibrotic scar secondary to nvAMD. METHODS:Macular findings in a white woman with untreated inactive subretinal fibrosis due to nvAMD in her right eye were documented over 9 years with color fundus photography (CFP), fundus autofluorescence (FAF) imaging, and optical coherence tomography (OCT). After death (age 90 years), this index eye was prepared for light and electron microscopy to analyze 7 discrete zones of pigmentation in the fibrotic scar. In additional donor eyes with nvAMD, we determined the frequency of black pigment (n = 36 eyes) and immuno-labeled for retinoid, immunologic, and microglial markers (RPE65, CD68, Iba1, TMEM119; n = 3 eyes). RESULTS:During follow-up of the index eye, black pigment appeared and expanded within a hypoautofluorescent fibrotic scar. The blackest areas correlated to melanotic cells (containing large spherical melanosomes), some in multiple layers. Pale areas had sparse pigmented cells. Gray areas correlated to cells with RPE organelles entombed in the scar and multinucleate cells containing sparse large spherical melanosomes. In 94% of nvAMD donor eyes, hyperpigmentation was visible. Certain melanotic cells expressed some RPE65 and mostly CD68. Iba1 and TMEM119 immunoreactivity, found both in retina and scar, did not co-localize with melanotic cells. CONCLUSION/CONCLUSIONS:Hyperpigmentation in CFP results from both organelle content and optical superimposition effects. Black fundus pigment in nvAMD is common and corresponds to cells containing numerous large spherical melanosomes and superimposition of cells containing sparse large melanosomes, respectively. Melanotic cells are molecularly distinct from RPE, consistent with a process of transdifferentiation. The subcellular source of spherical melanosomes remains to be determined. Detailed histology of nvAMD eyes will inform future studies using technologies for spatially resolved molecular discovery to generate new therapies for fibrosis. The potential of black pigment as a biomarker for fibrosis can be investigated in clinical multimodal imaging datasets.

IMPORTANCE/OBJECTIVE:Although the diagnosis of vitreoretinal lymphoma (VRL) can be challenging, early detection is critical for visual prognosis. OBJECTIVE:To analyze the spectrum of optical coherence tomography (OCT) findings in patients with biopsy-proven VRL and correlate these features with clinical parameters. DESIGN/METHODS:Retrospective cross-sectional study SETTING: Multicenter chart review from 13 retina, uveitis and ocular oncology clinics worldwide over an 11-year period (2008-2019). PARTICIPANTS/METHODS:Patients with a diagnosis of biopsy-proven VRL imaged with OCT at presentation EXPOSURE: The ocular information, systemic information and multimodal retinal imaging findings were collected and studied. MAIN OUTCOME MEASURE/METHODS:Characteristics of VRL on OCT RESULTS: A total of 182 eyes of 115 patients (63 women, mean age 65 years) were included in this study. The disease was bilateral in 81 (70%) patients, and mean baseline visual acuity (VA) was 0.2±0.89 logMAR (Snellen equivalent of 20/32). At baseline, 38 patients (33%) presented with isolated ocular involvement, 54 (45%) with associated central nervous system (CNS) involvement and 11 (10%) with other systemic lymphomatous involvement and an additional 12 (10%) patients presented with both CNS and other systemic involvement. On OCT, tumor infiltration was identified in various retinal layers including lesions in the sub-retinal pigment epithelium (RPE) compartment (91% of eyes), the subretinal compartment (43% of eyes) and the intraretinal compartment (7% of eyes). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:OCT analysis of eyes with vitreoretinal lymphoma identified 3 main regions of retinal infiltration. Sub-RPE location, with or without subretinal infiltration, was the most common pattern of involvement whereas isolated intraretinal infiltration was the least common.