Study sample

The diagnosis of RAP was based on previously described spectral domain OCT findings [21], including intraretinal HRF and fluid, with leakage confirmed by fluorescein angiography. All eyes were treatment-naïve at the time of diagnosis (Fig 1). In eyes with diabetic retinopathy and hard exudates, we only included treatment-naïve eyes with hard exudates in the avascular outer nuclear layer (ONL) in order to avoid other possible confounding structures such as microaneurysms, which may manifest as HRF in the vascularized layers. For patients with AMD, we included treatment- naïve eyes with intermediate or late dry AMD, exhibiting areas of RPE migration appearing as intraretinal HRF without intraretinal fluid or evidence of progression over the following period of 6 months. The diagnosis for these patients was made based on clinical assessment by a retina specialist (A.A.F).

A. Fluorescein angiogram during the late venous phase shows a hyperfluorescent leaking "hot spot" superior to the foveal avascular zone, corresponding to the RAP lesion. (red circle) B. Optical coherence tomography (OCT) cross section showing a hyperreflective intraretinal lesion. (red circle) C. En face optical coherence tomography angiography (OCTA) of the deep capillary plexus (DCP), shows an abnormal vascular structure superior to the foveal avascular zone. (cyan circle) D. OCTA cross section representing the DCP slab in (C), segmented with an upper boundary 30 μm below the inner plexiform layer (IPL), and a lower boundary set at 10 μm below the outer plexiform layer (OPL), shows flow signal starting within the hyperreflective lesion arising from the DCP and traversing the outer nuclear layer (ONL) to reach the RPE. (cyan circle) E. En face OCTA of the outer avascular retina, reveals a downward-growing extension of RAP from the overlying DCP. (yellow circle) F. OCTA cross section representing the outer slab in (E), segmented with an upper boundary set 10μm below the OPL and a lower boundary set at 10 μm above Bruch's membrane, shows flow signal corresponding to the RAP lesion. (yellow circle).

Only eyes that had OCTA images without significant movement or shadow artifacts, a quality index (Q) of 6 or more and a signal strength index (SSI) above 50 were considered eligible. Exclusion criteria were eyes with other retinal or choroidal diseases that may confound our results and eyes that have received intravitreal pharmacotherapy of any form, retinal laser or pars plana vitrectomy. We excluded eyes with astigmatism more than 3 diopters, high refractive errors (more than 6 diopters), or cataract graded above nuclear opalescence grade three or nuclear color grade three, to avoid optical artifacts that potentially may compromise OCTA image quality. Electronic medical records were reviewed to extract demographic and clinical information.