Choriocapillaris breakdown precedes retinal degeneration in age-related macular degeneration

Abstract

This work presents a combined light and electron microscopical approach to investigate the initial breakdown of the retinal pigment epithelium (RPE) and choriocapillaris (CC) in age-related macular degeneration (AMD). Perimacular sections of 12 dry and wet AMD eyes (82 ± 15 years) and 7 age-matched controls (75 ± 10 years) without retinal pathology were investigated. Disease progression was classified into 5 stages of retinal degeneration to investigate the concurrent CC breakdown. Special emphasis was laid on transitions where intact CC-RPE-retina complexes went over into highly atrophied areas. AMD sections showed elevated loss of photoreceptors, RPE and CC (p < 0.01), and thickened Bruch's membrane with increased basal laminar and linear deposits compared with controls. Up to 27% of the CC was lost in controls although RPE and retina were still intact. This primary loss of CC further increased with AMD (up to 100%). The data implicate that CC breakdown already occurs during normal aging and precedes degeneration of the RPE and retina with AMD, defining AMD as a vascular disease. Particular attention should be given to the investigation of early AMD stages and transitional stages to the late stage that reveal a possible sequence of degenerative steps with aging and AMD.

Optical Coherence Tomography Angiography Offers New Insights into Choriocapillaris Perfusion

“…Another study by Moult et al [48] found focal regions of CC flow alteration underlying nascent GA and drusen-associated GA as well as a diffuse CC flow impairment throughout the imaged field. These preliminary results underscore the theory that CC breakdown precedes RPE and photoreceptor degeneration [7]. CC flow impairment at the margin of GA may also be a potential predictor of GA growth with regards to both growth direction and growth rate [49].…”

“…The production of trophic factors, including vascular endothelial growth factor (VEGF) by the RPE, ensures CC survival, while CC atrophy results in tissue hypoxia accelerating RPE and photoreceptor dysfunction [5]. A recent histopathologic study by Biesemeier et al [7] suggests that changes in CC precede the degeneration of the RPE in AMD. Whether alterations in the CC are in fact the primary event in nonexudative AMD or secondary to molecular changes in the RPE is still a matter of debate.…”

“…If one is compromised, the other will follow, and eventually both layers may degenerate within a short time [3]. Changes in CC are known to occur physiologically with increasing age and to be associated with a wide range of retinal diseases such as age-related macular degeneration (AMD) and central serous chorioretinopathy (CSC), which are major causes of vision loss [4][5][6][7][8]. Thus, visualization and quantification of CC microvasculature and CC blood flow are of great interest.…”

Choroidal Flow Signal in Late-Onset Stargardt Disease and Age-Related Macular Degeneration: An OCT-Angiography Study

“…[21][22][23] In contrast, AMD as a multifactorial disease showed inconsistent histopathologic results as there may be transition zones from intact to absent CC as well as CC breakdown preceding outer retinal degeneration. 9,24,25 In this context, hypofluorescence in areas of RPE atrophy during late phases of indocyanine green angiography (ICGA), used to visualize choroidal vasculature, 26,27 was found to be more common in STGD1 compared to AMD. 28 The introduction of optical coherence tomography angiography (OCT-A) allows for noninvasive in vivo visualization of blood flow with three-dimensional resolution.…”

A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety and Surgical Outcomes

“…[1][2][3][4] The early and intermediate stages of the disease are characterized by the accumulation of drusen and a slow loss of the choriocapillaris. [5][6][7] Initially, both stages are associated with minimal impairment of visual acuity. 3,8,9 However, in advanced AMD, loss of vision can be caused by either exudative neovascular (''wet'') AMD or geographic atrophy (GA).…”