Suspended Scattering Particles in Motion: A Novel Feature of OCT Angiography in Exudative Maculopathies

Abstract

Objective: To characterize features of extra-vascular optical coherence tomography angiography (OCTA) signals corresponding to hyperreflective intraretinal fluid across various exudative maculopathies.

Design: Multicenter, retrospective, observational study.

Participants: Eyes with various forms of exudative maculopathy including diabetic retinopathy (DR), retinal vein occlusion (RVO), and neovascular-age related macular degeneration (nvAMD).

Methods: Patients with extra-vascular OCTA signal identified on en face OCTA images were included in this study. This signal was readily distinguishable from projection artifacts. The regions with the extra-vascular motion signal on OCTA were named "Suspended Scattering Particles in Motion (SSPiM)." Depth-encoded, color, en face OCTA images (3mm × 3mm) centered on the fovea and their corresponding structural OCT scans were used to quantify features of SSPiM and its corresponding hyperreflective fluid. Longitudinal data were collected when available.

Main outcome measures: Anatomic location, the association with hyperreflective material, changes in location and appearance of SSPiM over time, and replication of SSPiM OCTA signal in an in vitro phantom.

Results: Seventy-six eyes in 62 patients with various forms of exudative maculopathy were evaluated; 60 eyes with DR, 9 eyes with RVO, and 5 eyes nvAMD, 1 eye with macroaneurysm, and 1 eye with radiation retinopathy. Intraretinal accumulations of fluid with increased OCT signal intensity corresponded to regions of SSPiM in several exudative maculopathies. An in vitro phantom model demonstrates that particulate matter in suspension can generate similar OCTA signal. SSPiM showed an anatomic preference for vascular-avascular junctions. The hyperreflective fluid corresponding to SSPiM appeared more frequently in Henle's fiber layer (HFL) than the inner nuclear layer (INL) and was highly associated with hyperreflective material (HRM) found bordering the fluid. In five of eight longitudinal cases, the resolution of SSPiM resulted in the formation of confluent HRM. Clinically, this appeared as hard exudate on funduscopic images.

Conclusions: Clinical data suggest that SSPiM is a novel imaging feature of retinal vascular diseases that was not appreciated prior to the use of OCTA. We characterized several novel features of SSPiM and demonstrated that at least in some cases it resolves with residual hard exudate.

Figure 1

SSPiM and corresponding hyperreflective intraretinal fluid seen in various exudative maculopathies. All 3mm × 3mm depth-encoded color en face OCTA images with accompanying structural OCTs were captured using an SD-OCT (AngioPlex or Optovue) or SS-OCT (PlexElite) device. On depth-encoded images red corresponds to the superficial retinal layer, and green to the deep retinal layer. Structural OCTs above each en face image have superimposed OCTA signal (in red) to better distinguish the hyperreflective fluid. All yellow arrows point to hyperreflective fluid on structural OCTs and SSPiM on the en face images. (A) 53-year-old female with moderate NPDR and history of anti-VEGF treatment. Hyperreflective fluid is seen on the enlarged structural OCT in HFL and is bordered by HRM. The superficial foci of HRM is at the junction of HFL and the OPL whereas the deep foci of HRM rest above the ONL. The SSPiM on the en face image corresponding to the hyperreflective fluid begins at the border of the FAZ and extends peripherally (AngioPlex). (B) 68-year-old female with a moderate NPDR and history of anti-VEGF treatment. A central area of SSPiM corresponds with hyperreflective fluid with flow signal (AngioVue). (C) 70-year-old male with severe NPDR. A central area of hyperreflective fluid is accompanied by centrally located SSPiM. A smaller area of fluid on OCT can be appreciated in the ONL with corresponding SSPiM at the 3 o’clock border of the FAZ (AngioPlex). (D) 67-year-old female with PDR and history of PRP laser treatment. Hyperreflective fluid in HFL has corresponding SSPiM near the border of the FAZ (AngioPlex). (E) 67-year-old female with moderate branched retinal vein occlusion (BRVO) and known history of anti-VEGF treatment. A small pocket of hyperreflective fluid in HFL is bordered by foci of hyperreflective material. The corresponding SSPiM also exists as a small region on the border of the FAZ. There is additional SSPiM present in the en face image that falls outside of the structural OCT cross-section (AngioPlex). (F) 58-year-old female with hemi-retinal vein occlusion (HRVO). SSPiM is largely present in area affected by occlusion with corresponding hyperreflective fluid visible on structural OCT (PlexElite). (G) 77-year-old female with neovascular AMD and history of anti-VEGF treatment. The macula is slightly off-center in the 3mm × 3mm window with extensive SSPiM filling in the FAZ and its borders. A ring of HRM can be seen forming around the corresponding hyperreflective fluid on B-scan. (H) 65-year-old male with neovascular AMD and history of anti-VEGF treatment. A larger area of hyperreflective fluid is bordered by foci of hyperreflective material which appear to coalesce near the right side of the structural OCT image. The corresponding SSPiM is a large area on the border of the FAZ (AngioPlex).

Figure 2

Resolution of SSPiM associated with formation of hard exudate. This is a case of severe non-proliferative diabetic retinopathy in a 56-year-old-male followed over 7 months. His best corrected visual acuity at t = 0 months was 20/40 and at t = 7 months was 20/30. The patient has a history of focal laser treatment and multiple anti-VEGF injections. He received 3 injections during this 7-month period: aflibercept at t = 0 and 6 months, and dexamethasone at t = 3.5 months. The 3×3 depth-encoded, color, en face OCTA images with accompanying structural OCTs (A–C) were captured using an SD-OCT device. (A) Initially at t = 0 months there is a large area of hyperreflective fluid seen on structural OCT with corresponding SSPiM (yellow arrows). The green line represents the cross-section of the en face image where the structural OCT was obtained. This was taken in a similar location in each image using vascular landmarks. The SSPiM can be appreciated as red or green corresponding to depth. There is also a large hyporeflective pocket present in the structural OCT with no corresponding SSPiM (white arrows). (B) At t = 3.5 months there is an increasing number of foci of hyperreflective material that are beginning to coalesce as seen on structural OCT. There appears to be a decrease in SSPiM in areas corresponding to the development of hyperreflective material. (C) The SSPiM is mostly resolved with the exception of some signal in the center of the fovea. Abundant, confluent hyperreflective material is seen on structural OCT. The hyporeflective pocket has persisted with no corresponding SSPiM and no discernable development of hyperreflective material. (D) At t = 7 months the confluent hyperreflective material can be seen clinically as hard exudate on color fundus photography. (E–F) The hard exudate seen clinically corresponds to the area of hyperreflective material, as seen on Spectralis OCT. Of note, only a portion of the SSPiM on the en face image resolved into hard exudate clinically. For instance, the SSPiM near the 9 o’clock border of the 3mm × 3mm image resolved with no formation of hard exudate.

Figure 3

In vitro phantom of suspended particles imaged by OCTA. (A) Schematic of phantom with suspended particles in gel-like medium (purple) set in a solidified background composed of 0.4% TiO₂ particles and 25% gelatin. OCTA signal can be viewed in both cross-sectional (single B-scan) and en-face views. (B) OCTA signal is present when imaging 1% intralipid suspended in 1% gelatin solution in both cross-section (B-scan) and in en-face view. In contrast, there is no OCTA signal when imaging the control suspension, composed of pure gelatin with 0% intralipid or the background containing the solid TiO₂.