Faculty Bibliography

PURPOSE/OBJECTIVE:To provide an image-based description of retinal features associated with risk for development of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD), as visualized with multimodal imaging anchored by structural optical coherence tomography. DESIGN/METHODS:Consensus meeting METHODS: As part of the Classification of Atrophy Meeting program, an international group of experts analyzed and discussed retinal multimodal imaging features in eyes with AMD associated with GA and/or risk of progression to GA. Attendees undertook pre-meeting grading exercises that were reviewed during the meeting sessions. Meeting presentations illustrated established and investigational multimodal imaging features and associated histology. These different features were then each discussed openly by the entire group to arrive at consensus definitions. These definitions were applied to 40 additional images that were graded independently by attendees, to further refine the consensus definitions and descriptions. RESULTS:Consensus was reached on images with descriptors for 12 features. These features included components of outer retinal atrophy (e.g., ellipsoid zone disruption), components of complete retinal pigment epithelium (RPE) and outer retinal atrophy (e.g., RPE perturbation with associated hypo- or hyper-transmission), features frequently seen in eyes with atrophy (e.g., refractile drusen) and features conferring risk for atrophy development (e.g., hyperreflective foci, drusen, and subretinal drusenoid deposits). CONCLUSIONS:An International consensus on terms and descriptions was reached on multimodal imaging features associated GA and with risk for GA progression in eyes with AMD. We believe this information will be useful to clinicians who manage patients with AMD, researchers who study AMD disease interventions and pathogenesis, and those who design clinical trials for therapies targeting earlier AMD stages than GA expansion.

PURPOSE/OBJECTIVE:To study microvascular characteristics of small resolved paracentral acute middle maculopathy (PAMM) lesions in fellow eyes of patients with unilateral retinal vein occlusion (RVO). DESIGN/METHODS:Prospective cross-sectional study. PARTICIPANTS/METHODS:Patients with prior unilateral branch or central RVO and optical coherence tomography (OCT) evidence of resolved PAMM in their fellow, otherwise normal, eyes were prospectively recruited and imaged with OCT angiography (OCTA). METHODS:The resolved PAMM lesions were identified as focal areas of inner nuclear layer thinning over an anteriorly displaced outer plexiform layer (OPL). En face OCTA projections showing the location and size of the resolved PAMM lesions were created using 2 OPL segmentation lines with -9 μm and 0 μm offsets, and the cumulative distribution was evaluated. Anterior to the resolved PAMM lesions, vessels in the superficial vascular plexus were traced to identify small arterioles supplying the affected areas. MAIN OUTCOME MEASURES/METHODS:Cumulative spatial distribution on small resolved PAMM lesions. RESULTS:From 24 fellow eyes of 24 patients with unilateral RVO (15 males and 9 females, mean age 62.0 ± 15.1 years) 152 resolved PAMM lesions were identified. Of these lesions, 130 (85.5%) were found within the perifoveal region, and only 12 (7.9%) were found within the temporal quadrant. Of 28 lesions analyzed, the arteriole supplying the affected area was a single side branch of a larger vessel, with only 3 supplied by a terminal branch. CONCLUSION/CONCLUSIONS:Small resolved PAMM lesions in fellow eyes of patients with unilateral RVO are most prevalent in perifovea regions supplied by side branches of low order retinal arteries.

PURPOSE/OBJECTIVE:To describe the clinical and multimodal imaging (MMI) features of age-related macular degeneration (AMD) eyes presenting with intraretinal exudation and no evidence of neovascularization or structural alterations of native retinal vessels. METHODS:This was a retrospective review of the MMI and electronic health records for 3 consecutive patients presenting with unilateral exudative non-neovascular age-related macular degeneration. MMI included confocal color fundus photography (CFP), fundus autofluorescence (FAF), fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), swept-source optical coherence tomography angiography (SS-OCTA), and spectral domain optical coherence tomography angiography (SD-OCTA). Dense B-scan OCTA (DB-OCTA) patterns and implemented image post-processing were used to improve spatial resolution in the OCTA analysis and remove projection artifacts. RESULTS:Three eyes of 3 patients (1 male and 2 females, ages 72-87) developed intraretinal fluid (IRF) producing retinal edema during regular follow-up for non-neovascular AMD. FA, SS-OCTA, and DB-OCTA demonstrated no evidence of macular neovascularization or discrete retinal vascular abnormalities that could explain the IRF accumulation. Two eyes received intravitreal anti-VEGF therapy and demonstrated prompt resolution of IRF with periodic recurrences over time. CONCLUSION/CONCLUSIONS:Exudative non-neovascular AMD is a novel clinical phenotype characterized by the presence of non-neovascular intraretinal exudation producing macular edema. Differentiating this condition from other manifestations of AMD requires appropriate use of MMI. Further study is needed to assess the clinical impact and optimal management of exudative non-neovascular AMD.

PURPOSE/OBJECTIVE:To determine histologic correlates for defined stages of drusen-associated atrophy observed with multimodal imaging including fundus autofluorescence (FAF) and color fundus photography (CFP) of eyes with advanced age-related macular degeneration (AMD). DESIGN/METHODS:Case study and clinicopathologic correlation. SUBJECT/METHODS:A white woman in whom AMD findings of inactive subretinal fibrosis (right eye) and untreated non-exudative type 1 macular neovascularization (left eye) were followed for 9 years before death at age 90 years. METHODS:Eyes preserved 6.25 hours after death were post-fixed in osmium tannic acid paraphenylenediamine and prepared for sub-micrometer epoxy resin sections (n=115, 90 in right and left eyes, respectively), with 19 aligned to clinical OCT B-scans. Drusen visible by CFP at the last visit were assigned to 4 stages of in vivo FAF: Stage 1, isoFAF, no obvious FAF alteration; Stage 2, mildly uniform hyperFAF; Stage 3, a ring of hyperFAF around a center of hypoFAF; and Stage 4, uniform hypoFAF. MAIN OUTCOME MEASURES/METHODS:Light microscopic morphology at known FAF stages, including druse size, druse contents and changes in overlying retinal pigment epithelium (RPE), photoreceptors and external limiting membrane (ELM). RESULTS:Histology of 166 drusen demonstrated that stage 1 iso-FAF drusen were visible in CFP. HyperFAF in Stage 2 corresponded to short photoreceptors and complete coverage by RPE. HypoFAF in Stage 3 and 4 corresponded to different extents of RPE atrophy (RPE gap and no RPE, respectively). Of stage 4 drusen, 67% have no ONL and an undetectable ELM. Stage 4 includes a high proportion of refractile drusen (82%) with many calcific nodules, visible in CFP. CONCLUSION/CONCLUSIONS:This represents the first direct clinicopathologic correlation for FAF imaging of drusen-associated atrophy. Our data support 4 FAF stages of drusen-associated atrophy. Stage 2 is the earliest detected stage in which loss of screening by photoreceptor photopigment contributes to uniform hyperFAF. Stages 3 and 4 are consistent with incomplete RPE and outer retinal atrophy (iRORA) as defined by the Classification of Atrophy Meetings group. Loss of RPE, ONL and ELM in Stage 4 indicates that atrophy can begin over individual drusen. Our findings will help the identification of new therapeutic approaches and clinical study endpoints.

To describe a peculiar hyperreflective optical coherence tomography finding of nodular epiretinal gliosis at the fovea that may be a manifestation of Müller response to retinal injury. The central fovea is stabilized by the Müller cell cone but is at risk of foveal dehiscence due to various insults including vitreomacular traction which can lead to lamellar or full thickness macular hole formation.¹ Degenerative lamellar macular holes can be associated with epiretinal proliferation which has been attributed to activated Muller cells.² In this report, we describe a very unusual optical coherence tomography (OCT) finding of nodular epiretinal gliosis which may be the result of Müller cell activation and expansion.

PURPOSE/OBJECTIVE:To study the effect of the suspended scattering particles in motion (SSPiM) on optical coherence tomography angiography (OCTA) vessel density metrics in eyes with diabetic macular edema (DME) METHODS:: Thirty-four eyes with DME from 27 patients (16 males and 11 females, 61.4 ± 9.6 years) with DME were included in this retrospective cohort study. Among these eyes, 19 (55.9%) showed the SSPiM artifact on OCTA. All participants received 3-mm and 6-mm optical coherence tomography angiography (OCTA) imaging. Perfusion density and skeletonized vessel density were calculated for the superficial capillary plexus (SCP) and the deep capillary plexus (DCP), and these were compared between eyes with and without SSPiM. Additionally, foveal vessel density in a 300-µm-wide region around the foveal avascular zone (FVD) was evaluated on 3-mm OCTA scans. The main outcome measures were vessel density in the SCP and the DCP. RESULTS:Among the 3-mm OCTA images, there was no statistically significant difference in SCP vessel density in eyes with and without SSPiM (p = 0.98). Vessel density in the DCP (p = 0.001 and p = 0.028 for perfusion and skeletonized vessel density, respectively) and FVD (p = 0.03) on 3-mm OCTA scans were significantly higher in DME eyes with SSPiM than in those without SSPiM. There were no statistically significant differences in vessel density in SCP and DCP between eyes with and without SSPiM based on 6-mm OCTA scans. CONCLUSION/CONCLUSIONS:The presence of SSPiM may lead to an overestimation of DCP vessel density in eyes with DME when 3-mm OCTA scans are used for analysis.

PURPOSE/OBJECTIVE:To demonstrate the clinical and research value of a simplified technique enabling alignment of functional microperimetry data with retinal structure imaged by eye-tracked optical coherence tomography (OCT) in eyes with macular disease. METHODS:Normal and diseased eyes underwent sequential Spectralis OCT macular raster scans and Macular Integrity Assessment (MAIA) microperimetry using both standard central 10° analysis and custom scan patterns. The microperimetry data were imported into Spectralis research software which was automatically registered to the scanning laser ophthalmoscopy near-infrared reflectance image obtained during OCT acquisition. The OCT B-scans were directly correlated to the microperimetry data so that retina sensitivity (RS) and retinal microstructure at corresponding points could be evaluated simultaneously. RESULTS:Seventy eyes of 41 patients (110 studies) aged 22-95 years (mean 63.5 ± 18.0 years) with both normal and pathologic macular changes were included. The mean MAIA RS of all 110 studies was 22.2 ± 4.9 (range: 0.1 - 30.3). Retinal sensitivity showed good correspondence structural changes seen on OCT B-scans. CONCLUSIONS:We demonstrate a practical method to align RS data to anatomic tomographic findings. This technique provides data not obtainable with standard visual acuity measures.