To investigate the morphological changes of polyps in eyes with polypoidal choroidal vasculopathy (PCV) after treatment with vascular endothelial growth factor (VEGF) inhibitors using swept source optical coherence tomography angiography (SS-OCTA).
Following anti-VEGF therapy, polyps were found to evolve into typical type 1 macular neovascularization (MNV) in five eyes. In all of these five eyes, a polypoidal lesion was detected adjacent to a serous or hemorrhagic retinal pigment epithelial detachment (PED).
Conclusions and importance
Polypoidal lesions in PCV can evolve into typical type 1 MNV. This morphological evolution suggests that these polyps are clusters of tangled vessels that can proliferate into a more typical neovascular pattern, and this evolution may be facilitated by being adjacent to a PED. Since this morphological appearance could be associated with a better prognosis, SS-OCTA might be helpful in identifying cases of transformed polyps that may be associated with a decreased risk for vision loss.
Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration that affects a younger population. PCV is defined by the presence of type 1 macular neovascularization (MNV) characterized by branching vascular networks (BVNs) with polyp-like extensions. The natural course and prognosis of PCV is highly variable. , Some eyes with symptomatic PCV have a relatively benign course without treatment, and some even experience vision improvement. While in other cases, the disease progresses, and these polypoidal lesions can cause massive macular hemorrhages resulting in severe vision loss. The regression of polypoidal lesions is a promising sign in cases with better visual acuity outcomes and may serve as a positive prognostic indicator, while persistent clusters of grape-like polyps have a higher risk of bleeding, leakage, and worse visual outcomes. ,
Until the advent of optical coherence tomography angiography (OCTA), indocyanine green angiography (ICGA) was the gold standard for diagnosing PCV since Yannuzzi et al. first described the condition in 1990. , Currently, OCTA has revolutionized the way we follow up and manage patients with PCV because it is non-invasive, fast, safe, and easily repeatable. Compared with spectral domain OCTA (SD-OCTA), the longer wavelength used in swept source OCTA (SS-OCTA) results in improved lesion detection and allows for the detailed visualization of the polypoidal lesions and the BVNs. , The presence of BVN is thought to be synonymous with typical type 1 MNV.
Controversy persists as to whether the internal structure of polypoidal lesions represents aneurysmal diliatations, a tangled vascular network, or even a mixture of both morphologies. However, when following eyes with PCV after anti-vascular endothelial growth factor (VEGF) treatment, we observed an evolution in the appearance of some polypoidal lesions in response to treatment. In this case series, we used SS-OCTA to detect a morphological evolution of polypoidal lesions into a more typical appearance for type 1 MNV, and this evolution may be associated with improved prognosis in PCV eyes after anti-VEGF treatment.
SS-OCTA imaging (PLEX Elite 9000, Carl Zeiss Meditec, Dublin, CA) was performed using an instrument with a central wavelength of 1060 nm and a scanning rate of 100,000 A-scans per second. The choice of scanning pattern was at the discretion of the treating retina specialist and both 6 × 6 mm and 12 × 12 mm scan patterns were chosen to optimize the visualization of the entire PCV lesion. Both of these scan patterns consist of 500 A-scans per B-scan at 500 B-scan positions and each B-scan was repeated twice at each position, resulting in an A-scans and B-scans separation of 12 μm in 6 × 6 mm images and 24 μm in 12 × 12 mm images. FastTrac motion correction software was used while the images were acquired.
The RPE to RPE-fit slab was used to view the PCV complex. The built-in SS-OCTA segmentation editing software was used to manually correct the segmentation boundaries if needed. When using the RPE to RPE-fit slab, we reviewed the en face angiographic and structural images, as well as the corresponding B-cans, to detect both the flow and structural profiles consistent with a PCV lesion. Polyps were recognized as flow signals underlying a dome-shaped peaked retinal pigment epithelial detachment (PED) on B-scans with en face images corresponding to a configuration previously observed using en face ICGA imaging. BVNs were recognized as vascular patterns on en face flow and structural images corresponding to the double-layer sign with a flow signal detected on the cross-sectional B-scans.
The criteria for reinjection was based on the persistence, increase, or recurrence of intraretinal and/or subretinal fluid on structural OCT. Eyes were considered to have a good prognosis based on the absence or decrease of macular fluid on structural OCT scans and based on their final vision compared with the baseline vision.
A 57-year-old Hispanic man with a diagnosis of PCV in his left eye presented with a new onset hemorrhage. The visual acuity (VA) of the left eye was 20/400. His left eye had received 15 previous anti-VEGF injections before both fluorescein angiography (FA) and ICGA imaging were performed ( Fig. 1 A, B). FA confirmed a hemorrhagic PED adjacent to an area of hyperfluorescent leakage and ICGA imaging showed that this area of hyperfluorescence corresponded to a cluster of multi-focal hyperfluorescent polyps consistent with PCV ( Fig. 1 B). After three monthly injections of anti-VEGF therapy (aflibercept), vision improved to 20/150. At this time the SS-OCTA en face flow image and the corresponding cross-sectional B-scan showed the polypoidal lesion as a dense round vascular structure underneath the margin of the retinal pigment epithelial detachment (PED) ( Fig. 1 C, E). The left eye received 26 additional aflibercept injections over the following three years and the vision improved to 20/70. The most recent SS-OCTA image showed that the polypoidal lesion evolved into a shallow irregular PED, with the typical appearance of a double-layer sign corresponding to a BNV or type 1 MNV ( Fig. 1 D, F).
A 38-year-old Caucasian woman was diagnosed as PCV in her right eye in 2008 with a visual acuity of 20/30. Her right eye was treatment-naïve at presentation. The color fundus imaging in 2008 showed an orange nodule and an adjacent hemorrhagic PED ( Fig. 2 A). ICGA at that time confirmed the existence of the polypoidal lesion ( Fig. 2 B). In June 2016, after receiving 28 bevacizumab injections, SS-OCTA images showed that the polypoidal lesion had extended beneath the PED and had grown as a delicate vascular network over the previous 8 years ( Fig. 2 C, E). In addition, a new polypoidal lesion with an adjacent PED was detected at the margin of the neovascular complex. The vision in right eye was 20/40. In February 2020, after 26 more injections (3 bevacizumab and 23 aflibercept), the vision improved to 20/25. SS-OCTA images showed a low-lying type 1 neovascular network at the location where the polypoidal lesion had existed four years before ( Fig. 2 D, F).
A 67-year-old Asian man complained of blurry vision in his treatment-naïve right eye, which had been diagnosed 18 years previously with central serous chorioretinopathy (CSCR) with spontaneous resolution. His vision was now 20/30 in the right eye. FA and ICGA were performed to establish the diagnosis ( Fig. 3 A, B). The early phase FA showed a subtle smokestack plume consistent with CSCR. However, ICGA showed focal hyperfluorescence consistent with a polypoidal lesion at the nasal margin of the PED. The SS-OCTA en face flow image and the corresponding cross-sectional B-scan image showed the polypoidal lesion as a tangled vascular structure beneath the PED ( Fig. 3 C, E). The patient was given three anti-VEGF injections (ranibizumab) on a monthly basis and then observed for 11.5 months. His vision improved to 20/20 in the most recent visit and the SS-OCTA en face image showed a vascular network consitent with type 1 MNV ( Fig. 3 D, F). The corresponding cross-sectional B-scan showed a typical type 1 neovascular lesion under a low-lying PED.