Exudative non-neovascular age-related macular degeneration

Abstract

Purpose 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 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 nonneovascular AMD.

Pathways of Fluid Leakage in Age Related Macular Degeneration

“…Additional pathways to consider include ischemic RPE migration into the retina (i.e., intraretinal hyperreflective foci), driven by inner choroidal ischemia (as evidenced by choriocapillaris flow deficits with OCTA) and higher levels of intraretinal VEGF leading to increased retinal vascular permeability and leakage of fluid. 14…”

“…It is important to understand that both IRF and SRF can be the result of nonneovascular pathways in the context of AMD. [9][10][11][12][13][14] The presence of IRF and SRF with OCT does not always indicate neovascular activity and can be a sign instead of degenerative mechanisms. Pseudocysts were originally described by Cohen et al 15 and represent a form of IRF overlying the areas of retinal pigment epithelium (RPE) atrophy and cRORA (complete RPE and outer retinal atrophy).…”

“…However, recent studies have provided insight into the various nonneovascular pathways of exudation in eyes with AMD and indicate that fluid can have a much more complex and nuanced etiology and is not always an indicator of neovascular activity in AMD. [9][10][11][12][13][14] Although some have labelled nonneovascular fluid as a transudate and neovascular fluid as an exudate, 11,13 the mechanisms may be more complicated, and therefore, any form of fluid leakage (neovascular or nonneovascular) is best referred to as exudation. The subsequent sections of this editorial will summarize the various nonneovascular pathways of exudation (examples of exudation include IRF, SRF, and/or vitelliform lesions) in AMD and will provide guidelines for the diagnosis and management of nonneovascular fluid.…”

Macular Vascular Imaging and Connectivity Analysis Using High-Resolution Optical Coherence Tomography

“…We found that DCP draining venules were the largest connecting vessels crossing the INL and angled toward the target superficial vein. The DCP draining venules have been associated with the pathophysiology of diverse macular vascular disorders, including acute macular neuroretinopathy, 30 exudative nonneovascular age-related macular degeneration, 31 and branch retinal vein occlusion (RVO). 13 In eyes with RVO, the sequalae of ischemia and vascular remodeling have been used to explore blood flow circuitry within the retina.…”

Perifoveal Vascular Anomalous Complex and the spectrum of degenerative microvascular macular diseases

“…Recently, other macular disorders, characterized by the presence of exudation, have been reported in patients with AMD but in the absence of neovascularization. 27,28 These forms are characterized by subretinal and/or intraretinal fluid but without signs of MNVs. To describe exudative nonneovascular AMD, Hilely et al 27 reported three different phenotypes of subretinal fluid in patients with drusenoid pigment epithelium detachment without MNV.…”