Faculty Bibliography

PURPOSE: To describe a patient who showed progression of age-related macular degeneration along the course of an underlying large choroidal vessel. METHODS: Retrospective case report. RESULTS: An 84-year-old woman was diagnosed with age-related macular degeneration and followed for more than 6 years. Retinal pigment epithelial changes were more advanced in her right eye which had a thinner choroid than the fellow left eye. Multimodal imaging with swept-source optical coherence tomography showed that the progression of outer retinal and retinal pigment epithelial changes appeared to follow the course of a large choroidal vessel. CONCLUSION: The authors hypothesize that large choroidal vessels can compress the overlying choriocapillaris, possibly leading to outer retinal ischemia, which subsequently could focally accelerate the course of age-related macular degeneration.

PURPOSE: To report a posterior segment phenotypic manifestation of Coxsackie virus infection that has not been previously appreciated. METHODS: The clinical course and multimodal imaging findings, including spectral domain optical coherence tomography, fluorescein angiography, near infrared reflectance, and fundus autofluorescence of two patients with Coxsackie virus infections were documented. RESULTS: A neurosensory macular detachment was present in both patients on baseline examination. Fluorescein angiography demonstrated pooling within this lesion and spectral domain optical coherence tomography identified thickening of the retinal pigment epithelial band with variable degrees of attenuation of the ellipsoid zone and interdigitation zone. Fundus autofluorescence and near infrared reflectance imaging revealed multiple satellite lesions adjacent to the neurosensory detachment. These lesions were not seen on fluorescein angiography or color photography. Satellite lesions were hyporeflective on near infrared reflectance imaging and hyperautofluorescent on fundus autofluorescence imaging. The satellite lesions correlated with sites of ellipsoid disruption on spectral domain optical coherence tomography. Both patients were observed and their condition improved over the course of time. There was total resolution of satellite lesions, reconstitution of the ellipsoid zone and interdigitation zone, and return of retinal pigment epithelial thickness to the normal range. A bull's eye pattern of macular retinal pigment epithelial disturbance persisted on color and near infrared reflectance images, despite good visual acuity. CONCLUSION: Posterior segment Coxsackie virus infection may concurrently express the clinical characteristics of acute idiopathic maculopathy and multifocal retinitis. The visual prognosis in this variant is usually favorable. The multimodal imaging features that characterize this entity should be recognized to avoid confusion with other diseases that have a similar presentation.

PURPOSE: To report a case of focal choroidal excavation and choroidal neovascularization in the setting of pachychoroid disease. METHODS: Multimodal imaging, including fundus photography, fundus autofluorescence, enhanced depth imaging optical coherence tomography, indocyanine green angiography, and en face structural and angiographic optical coherence tomography. RESULTS: The authors describe a 39-year-old female with moderately high myopia presenting with focal choroidal excavation and associated choroidal neovascularization. Multimodal imaging demonstrated pachychoroid features with dilated choroidal vessels surrounding the lesion. Optical coherence tomography angiography showed Type 2 neovascularization. CONCLUSION: Some cases of focal choroidal excavation and associated neovascularization may be related to structural abnormalities of the associated choroidal vasculature.

BACKGROUND: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare, paraneoplastic syndrome characterized by bilateral painless visual loss and proliferation of choroidal melanocytes in association with an underlying systemic malignancy. We report a case of bilateral diffuse uveal melanocytic proliferation associated with an underlying gynecological malignancy that also features the infrequent finding of an iris mass lesion, using multimodal imaging including ultra-widefield imaging, spectral domain and swept-source optical coherence tomography. CASE PRESENTATION: A 59-year-old white female with a prior history of gynecological malignancy in remission presented with progressive bilateral visual loss over several weeks. The patient was noted to have a focal iris mass lesion in her right eye. Ultra-widefield color fundus photography showed a characteristic bilateral 'giraffe pattern' of pigmentary changes extending into the periphery as well as multiple discrete deeply pigmented lesions. Ultra-widefield autofluorescence was useful for visualizing the full extent of involvement. Indocyanine green angiography helped to demarcate the discrete pigmented choroidal lesions. Swept-source OCT clearly delineated the alternating zones of retinal pigment epithelium (RPE) thickening and RPE loss, as well as the prominent choroidal infiltration and thickening. CONCLUSIONS: BDUMP is an important diagnosis to consider in the presence of multiple discrete melanocytic choroidal lesions, diffuse choroidal thickening, characteristic RPE changes, iris mass lesions and exudative retinal detachment. Ultra-widefield imaging may demonstrate more extensive lesions than that detected on clinical examination or standard field imaging. Imaging with SS-OCT shows choroidal and RPE characteristics that correlate well with known histopathology of this entity.

PURPOSE: To determine the proportion of shallow irregular pigment epithelial detachments in eyes with pachychoroid features that harbor neovascular tissue and to study the morphology of this tissue with optical coherence tomography (OCT) angiography. DESIGN: Prospective consecutive cohort study. METHODS: Patients with pachychoroid spectrum diagnoses and shallow irregular pigment epithelial detachment in at least one eye (study eye) were included. Charts and multimodal imaging were reviewed to determine a dye-angiography detection rate for type 1 neovascularization in study eyes. All patients then underwent OCT angiography prospectively followed by masked segmentation and grading. RESULTS: 22 eyes of 16 patients were included. Mean age was 71 years (range 57-95). Mean subfoveal choroidal thickness was 381mum (SD: 141mum). Four out of 22 (18%) study eyes exhibited polypoidal lesions. Dye-angiography demonstrated specific features of neovascularization in 5 out of 17 (29%) eyes with suspected non-polypoidal pachychoroid neovasculopathy. With OCT angiography, type 1 neovascular tissue was visualized in 21 out of 22 (95%) study eyes. CONCLUSIONS: Our data suggest that, in eyes with pachychoroid features, the finding of a shallow irregular pigment epithelial detachment on OCT has greater diagnostic value for type 1 neovascularization than previously thought and that dye-angiography may underestimate the prevalence of neovascularization compared to OCT angiography.

IntroductionParacentral acute middle maculopathy (PAMM) has been described as an ischemic lesion of the middle retinal layers with a characteristic lamellar hyper-reflective placoid appearance in the acute phase and thinning of the involved retinal layers in the chronic phase. Optical coherence tomographic angiography (OCTA) is a novel and non-invasive technique for imaging retinal capillary vasculature with en face segmentation capabilities.MethodCase series. We describe two patients with PAMM who underwent clinical examination and multimodal imaging including OCTA.ResultsIn the first patient, who presented with PAMM secondary to acute cilioretinal artery occlusion, OCTA demonstrated reduction in flow in the deep capillary plexus (DCP). One month later, OCTA revealed a flow void due to thinning of the GCL, INL, and OPL and paradoxical apparent ONL thickening. Similar findings of focal retinal lamellar ectopia were seen in the second patient, who had an incidentally detected chronic PAMM lesion.ConclusionsOCTA images the superficial and deep capillary plexi independently. PAMM is characterized by acute and chronic attenuation of the DCP flow signature. Focal lamellar ectopia in PAMM is discussed.Eye advance online publication, 18 September 2015; doi:10.1038/eye.2015.180.

PURPOSE: To correlate postmortem histology with previously recorded multimodal imaging from a patient with type 1 neovascularization associated with an acquired vitelliform lesion in the setting of age-related macular degeneration (AMD). DESIGN: Case study. METHODS: Multimodal imaging that was obtained ante mortem was matched with ex vivo and high-resolution histological images of the preserved donor macula. Anatomic correlates for multimodal imaging findings were then defined. RESULTS: Spectral-domain optical coherence tomography (OCT) revealed a split in the retinal pigment epithelial-Bruch's membrane band. Type 1 NV in this case was comprised of 6 layered components: (1) Retinal pigment epithelium, (2) Basal laminar deposits, (3) Fibrovascular membrane, (4) Fibrocellular scar, (5) Hemorrhage, and (6) Bruch's membrane. The anatomic correlates for the hyporeflective band on spectral-domain OCT included a thick basal laminar deposit. Not all structures could be readily separated on the basis of their reflectivity patterns. CONCLUSIONS: This is an important clinicopathologic correlation of NV secondary to AMD in the spectral-domain OCT era. Our findings of 6 layers include and extend the anatomical framework encapsulated by the double-layer and triple-layer signs. The resolution of current devices does not always permit distinction of the different layers of NV tissue. Thick basal laminar deposits may appear hyporeflective on spectral-domain OCT and may be confused with fluid from a neovascular process. It will be important to perform a larger clinicopathologic series to aid our anatomical interpretation of spectral-domain OCT images.

PURPOSE: To investigate the frequency, natural evolution, and histologic correlates of layered, hyperreflective, subretinal pigment epithelium (sub-RPE) lines, known as the onion sign, in neovascular age-related macular degeneration (AMD). DESIGN: Retrospective observational cohort study and experimental laboratory study. PARTICIPANTS: Two hundred thirty eyes of 150 consecutive patients with neovascular AMD and 40 human donor eyes with histopathologic diagnosis of neovascular AMD. METHODS: Spectral-domain optical coherence tomography (SD OCT), near-infrared reflectance (NIR), color fundus images, and medical charts were reviewed. Donor eyes underwent multimodal ex vivo imaging, including SD OCT, before processing for high-resolution histologic analysis. MAIN OUTCOME MEASURES: Presence of layered, hyperreflective sub-RPE lines, qualitative analysis of their change in appearance over time with SD OCT, histologic correlates of these lines, and associated findings within surrounding tissues. RESULTS: Sixteen of 230 eyes of patients (7.0%) and 2 of 40 donor eyes (5.0%) with neovascular AMD had layered, hyperreflective sub-RPE lines on SD OCT imaging. These appeared as refractile, yellow-gray exudates on color imaging and as hyperreflective lesions on NIR. In all 16 patient eyes, the onion sign persisted in follow-up for up to 5 years, with fluctuations in the abundance of lines and association with intraretinal hyperreflective foci. Patients with the onion sign disproportionately were taking cholesterol-lowering medications (P = 0.025). Histologic analysis of 2 donor eyes revealed that the hyperreflective lines correlated with clefts created by extraction of cholesterol crystals during tissue processing. The fluid surrounding the crystals contained lipid, yet was distinct from oily drusen. Intraretinal hyperreflective foci correlated with intraretinal RPE and lipid-filled cells of probable monocytic origin. CONCLUSIONS: Persistent and dynamic, the onion sign represents sub-RPE cholesterol crystal precipitation in an aqueous environment. The frequency of the onion sign in neovascular AMD in a referral practice and a pathology archive is 5% to 7%. Associations include use of cholesterol-lowering medication and intraretinal hyperreflective foci attributable to RPE cells and lipid-filled cells of monocyte origin.

PURPOSE: To describe the use of optical coherence tomography angiography (OCT-A) for evaluating the spectrum of polypoidal vascular diseases. METHODS: Retrospective observational case series of seven patients with polypoidal choroidal vasculopathy (three cases) or polypoidal choroidal neovascularization (four cases). Optical coherence tomography angiography information was acquired using two different OCT-A devices (the Optovue RTVue XR Avanti SD-OCT and the Spectralis OCT angiography). Flow signals within branching vascular networks, type 1 neovascularization and polyps were evaluated. Comparisons were made between en face and cross-sectional OCT-A images. Vascular information from OCT-A was also compared with indocyanine green angiography. RESULTS: En face images from OCT-A provided anatomical information about branching vascular networks that were comparable to indocyanine green angiography. Polyps were poorly resolved on en face OCT-A images but were clearly defined on cross-sectional OCT-A images. Cross-sectional OCT-A revealed flow signals within focal regions of the polyps with a significant portion of the polyp lumen being devoid of flow signal. Flow signals from cross-sectional OCT-A images also showed that branching vascular networks, type 1 neovascularization, and polyps were confined to the anatomic compartment between the retinal pigment epithelium and Bruch's membrane. It was not possible to detect leakage on en face or cross-sectional OCT-A. CONCLUSION: The combination of en face and cross-sectional OCT-A images provides anatomical information about polypoidal structures that is comparable to indocyanine green angiography. OCT-A may be a useful modality for the management of polypoidal diseases. However, the limitations of OCT-A identified in this study suggest that it is not a replacement for indocyanine green angiography.

PURPOSE: To characterize the vascular structure of Type 3 neovascularization secondary to age-related macular degeneration using optical coherence tomography angiography. METHODS: Optical coherence tomography angiography cube scans (3 mm x 3 mm) were acquired in 29 eyes of 24 patients with Type 3 lesions secondary to age-related macular degeneration using the RTVue XR Avanti with AngioVue, Split-spectrum amplitude-decorrelation, and motion correction technology. Automated layer segmentation boundaries were adjusted to best visualize the neovascular complex on en face projection images. RESULTS: A distinct neovascular complex could be identified in 10 (34%) eyes, all of which were active on optical coherence tomography imaging. In all 10 eyes, the neovascular complex appeared as a small tuft of bright, high-flow tiny vessels with curvilinear morphology located in the outer retinal layers with a feeder vessel communicating with the inner retinal circulation (i.e., deep retinal capillary plexus). The mean (SD) size of the neovascular complex measured 0.07 (+/- 0.07) mm. CONCLUSION: With optical coherence tomography angiography, it is possible to identify small intraretinal neovascular complexes communicating with the deep retinal capillary plexus in eyes with Type 3 neovascularization secondary to age-related macular degeneration. Qualitative and quantitative analyses of Type 3 neovascular complexes can be performed using optical coherence tomography angiography.