Relationship between RPE and Choriocapillaris in Age-Related Macular Degeneration

Abstract

Purpose The purpose of this study was to examine the relationships between choriocapillaris (CC) and retinal pigment epithelial (RPE) changes in age-related macular degeneration (AMD). Morphological changes in the RPE/choriocapillaris complex were quantified in dry and wet forms of AMD and the results compared to with aged control eyes without maculopathy. Methods Postmortem choroids from 3 aged control subjects, 5 geographic atrophy (GA) subjects and 3 wet AMD subjects were analyzed using a semi-quantitative computer-assisted morphometric technique developed to measure percent RPE and CC areas in choroidal whole mounts incubated for alkaline phosphatase activity. The tissues were subsequently embedded in methacrylate and sectioned to examine structural changes. Results There was a linear relationship between the loss of RPE and CC in GA. A 50% reduction in vascular area was found in regions of complete RPE atrophy. Extreme constriction of remaining viable capillaries was found in areas devoid of RPE. Adjacent to active choroidal neovascularization (CNV) in wet AMD, CC dropout was evident in the absence of RPE atrophy resulting in a 50% decrease in vascular area. Lumenal diameters of the remaining capillaries in wet AMD eyes were similar to controls. Conclusions The primary insult in GA appears to be at the level of the RPE and there is an intimate relationship between RPE atrophy and secondary CC degeneration. CC degeneration occurs in the presence of viable RPE in wet AMD. The RPE in regions of vascular dropout are presumably hypoxic, which may result in an increase in VEGF production by the RPE and stimulation of CNV.

Retinal and Choroidal Thickness in Early Age-Related Macular Degeneration

“…Histological studies have been carried out to investigate the cross-sectional area and thickness of the choriocapillaris of donor eyes from individuals with early and advanced AMD. [14][15][16] Our data are in agreement with a study reporting a significant decrease in choriocapillary density in 25 eyes with features of AMD, but finding no significant decrease in the thickness of the choroid compared to age-matched controls. 14 Our data are also supported by a recent study by Chung et al (2011) evaluating choroidal thickness in early AMD using the 870nm OCT with an enhanced depth imaging technique.…”

“…23 However, there is evidence to suggest that choroidal thinning may occur in end-stage AMD. [15][16]23 McLeod et al examined the post-mortem choroid in 3 aged control eyes, 5 with geographic atrophy, and 3 with neovascular AMD and reported a linear relationship between the loss of RPE and choriocapillaris in geographic atrophy, and a 50% reduction in choroidal vascular cross-sectional area in eyes with wet AMD, even in the absence of RPE atrophy. 15 Sarks carried out a histological study on 378 eyes from patients aged 43-97 years, who had either normal fundi or some degree of AMD.…”

The stereotypical molecular cascade in neovascular age-related macular degeneration: the role of dynamic reciprocity

“…38,63 Yet, it is not inconceivable that there are localized micropockets of hypoxia in what is essentially the diseased microenvironment of the submacula and this will trigger the initial inflammation, as outlined in the previous section, that is required to promote an ECM conducive to supporting NV. [64][65][66][67] Alternatively, stabilization of hypoxic-inducible factor (HIF)-1 and, therefore, the promotion of NV may be triggered by the AMDassociated pathological oxidative stress within the RPE and photoreceptors, and this in turn will provoke the necessary initial inflammation that primes repair and leads to NV. 23,68,69 Moreover, activation of HIF transcription factors are being increasingly implicated in inflammation, repair, fibrosis, and epithelial-tomesenchymal transition, all pivotal features of chronic inflammatory diseases, including AMD.…”

An Effective Multi-Scales Interpolating and Enhancing Choroidal Vessels Segmentation Method

“…The choroidal vessels provide oxygen and nourishment to the outer retinal layers, and are crucial for metabolic activity in the retina [1]. Choroidal vessels changes are associated with some eye diseases, such as age-related macular degeneration (AMD), age-related choroidal atrophy, and choroiditis etc.…”

“…The choroidal vessels are vascular plexus between the retina and sclera that forms a vascular network, and they can be divided as the choriocapillaris [3] and the choroidal stroma [1,4,5]. The choroidal vessels are affected by many diseases of the retina, the changes of the choroidal vessels have been described as early macular degeneration and decreased choroidal vasculature thickness has been described in age-related macular degeneration [1,2,6]. Other diseases, such as polypoidal choroidal vasculopathy, and choroiditis, are associated with the choroidal vessels.…”