Faculty Bibliography

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.

PURPOSE: To describe a possible causal association between the position of perforating scleral vessels and the position of lacquer cracks in eyes with pathologic myopia. DESIGN: Retrospective case series. METHODS: Medical records and multimodal imaging results, including confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography, were reviewed from patients with lacquer cracks secondary to pathologic myopia who presented between 2010 and 2014 to two institutions. Main outcome measure were the prevalence of perforating scleral vessels at the site of the lacquer crack, the position of the lacquer crack within the macula and the relationships between perforating scleral vessels and retinal-choroidal structures. RESULTS: A total of 35 eyes of 30 patients with lacquer cracks were included. The average number of lacquer cracks was 1.2+/-0.5/eye and in 37 out of 45 lacquer cracks (82%) retrobulbar vessels were found to perforate the sclera at the site of the lacquer crack. Lacquer cracks were more prevalent in the central macula (51%), than in the nasal (19%), temporal (14%), inferior (11%) and superior (5%) macula (P = 0.001). Transverse En Face images through the area of lacquer cracks were available for 8 cases and clearly depicted the perforating vessel's course through the sclera and its termination in the choroid, directly beneath the lacquer cracks. CONCLUSIONS: Perforating scleral vessels are often present beneath the site at which lacquer cracks form in pathologic myopia. We hypothesize that scleral expansion at the location of these perforating vessels may play a role in the formation of lacquer cracks.

BACKGROUND AND OBJECTIVE: To demonstrate a vascular pattern seen on optical coherence tomography angiography (OCTA) that appears to correlate with reduced rates of geographic atrophy (GA) in eyes receiving long-term anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Non-consecutive, retrospective cohort study. Patients were included if they had received more than 50 anti-VEGF injections during a period of at least 4 years for neovascular AMD in at least one eye, with absence or minimal progression of GA. Clinical charts and imaging were reviewed retrospectively; study eyes underwent OCTA. RESULTS: Nine eyes of eight patients were included. Mean age was 82 years, and mean follow-up of study eyes 9.1 years; study eyes received a mean of 65.8 injections. OCTA revealed tangled networks of neovessels associated with type 1 lesions. CONCLUSION: With prolonged anti-VEGF treatment, GA appears to occur less commonly in eyes with type 1 neovascularization. OCTA shows mature tangled vessels with substantial flow within type 1 lesions. Mature, tangled networks may be associated with a decreased likelihood of developing GA despite the presence of choriocapillaris atrophy. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:907-912.].

PURPOSE: To assess change in intraocular pressure (IOP) in patients with neovascular age-related macular degeneration (NVAMD) receiving intravitreal aflibercept injection (IAI) or ranibizumab in VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2 studies. DESIGN: Analyses from 2 randomized, active-controlled, phase III trials. PARTICIPANTS: A total of 2457 patients with NVAMD. METHODS: Patients received IAI 2 mg every (q) 4 weeks (2q4), 0.5 mg q4 weeks (0.5q4), 2 mg q8 weeks (after 3 monthly doses; 2q8), or ranibizumab 0.5 mg q4 weeks (Rq4) for 52 weeks. At week 52, patients were switched to a variable regimen requiring at least quarterly dosing and allowing interim injections based on anatomic and visual assessment. MAIN OUTCOME MEASURES: Pre-injection IOP was analyzed in study and uninjected fellow eyes from baseline to week 96. Prespecified end points included mean change in IOP from baseline and prevalence of a >21 mmHg and >10 mmHg increase in IOP from baseline. Cumulative incidence of sustained (at 2 consecutive visits) IOP >21 mmHg, a single event of IOP >25 mmHg, and sustained IOP increase from baseline (>/=5 mmHg) was also evaluated. RESULTS: Mean IOP change from baseline over 96 weeks in all IAI groups was consistently lower than in the Rq4 group, and this finding was replicated in both trials. In an analysis integrating both studies, the proportion of study eyes with IOP >21 mmHg at week 96 was 20.2%, 14.2%, 12.1%, and 12.5% in Rq4, 2q4, 2q8, and 0.5q4, respectively. Reduction in risk, relative to Rq4, of having sustained IOP >21 mmHg over 96 weeks was 62% (95% confidence interval [CI], 36%-78%), 50% (95% CI, 19%-70%), and 69% (95% CI, 45%-84%) for 2q4, 2q8, and 0.5q4, respectively. Risk reduction in the IAI groups for a sustained IOP increase >/=5 mmHg was 31% (95% CI, 8%-48%), 38% (95% CI, 17%-54%), and 47% (95% CI, 27%-61%), respectively. In uninjected fellow eyes, only sustained IOP >21 mmHg events were higher in the Rq4 group compared with all IAI groups. CONCLUSIONS: Incidence of elevated IOP in eyes with NVAMD was lower in all IAI groups than in the ranibizumab group.