Choriocapillaris Flow Imbalance in Fellow Eyes in Age-Related Macular Degeneration

Abstract

Purpose The purpose of this study was to identify early changes in choriocapillaris flow in patients with age-related macular degeneration (AMD) with no history of macular neovascularization (MNV). Methods Clinical records of fellow eyes of patients with unilateral neovascular AMD without fundus findings and control eyes of otherwise healthy individuals, except for mild cataract, diagnosed at St. Luke's International Hospital from April 2020 to March 2021, were retrospectively analyzed. Optical coherence tomography (OCT) angiography images of the choriocapillaris slab were binarized using the Phansalkar local thresholding methods to evaluate the choriocapillaris flow area (CCFA) and its coefficient of variation (CV). Results The data of 24 AMD fellow eyes (17 for men, 71.7 ± 1.9 years old) and 21 control eyes (11 for men, 69.1 ± 2.0 years old) were analyzed. The mean CCFA ratio was lower in the AMD fellow eyes (58.6 ± 1.2%) than in the control eyes (62.4 ± 1.3%, P = 0.032), and the mean CV of CCFA ratio was greater in the AMD fellow eyes (0.174 ± 0.007) than in the control eyes (0.154 ± 0.007, P = 0.032). Eyes with CCFA ratio <60% and CV of CCFA ratio ≥0.154 had a 4.371-fold higher risk of being AMD fellow eyes (95% confidence interval = 1.029–18.56, P = 0.046). Differences in CV of CCFA ratio between AMD fellow eyes and control eyes were particularly clear in eyes with thick choroids (mean CV of CCFA in control versus AMD fellow eyes with central choroidal thickness ≥220 µm: 0.144 ± 0.005 vs. 0.173 ± 0.007, P = 0.009**). Conclusions Neovascular AMD fellow eyes without MNV had reduced, heterogeneous, and imbalanced choriocapillaris flow, which may constitute early changes in neovascular AMD, although further studies are required.

Diabetic choriocapillaris flow deficits affect the outer retina and are related to hemoglobin A1c and systolic blood pressure levels

“…The cut-off values for choriocapillaris flow impairment in the current study were similar to our previous papers comparing eyes of control healthy patients and fellow eyes of unilateral age-related macular degeneration (AMD); the eyes with CCFA ratio < 60.0% and CV of the CCFA ratio ≥ 0.154 had an AMD risk 16 . So, these parameters would be of value to estimate the disease risk.…”

“…According to one post-mortem study, capillary dropout in the choriocapillaris of patients with diabetes is due to an increased number of polymorphonuclear leukocytes in the vascular lumen 23 . Heterogeneity of the choriocapillaris flow were similar to the changes which we reported in the fellow eyes of patients with unilateral age-related macular degeneration 16 , 17 , wherein low-grade chronic inflammation is known to be involved in the pathogenesis 24 , 25 . Diabetes is a chronic inflammatory disease 26 , and the heterogeneous progression of flow deficits may most likely reflect disease progression in response to systemic inflammatory conditions and not to focal stimuli.…”

Diabetic choriocapillaris flow deficits affect the outer retina and are related to hemoglobin A1c and systolic blood pressure levels

“…The cut-off values for choriocapillaris flow impairment in the current study were similar to our previous papers comparing eyes of control healthy patients and fellow eyes of unilateral age-related macular degeneration (AMD); the eyes with CCFA ratio < 60.0% and CV of the CCFA ratio ≥ 0.154 had an AMD risk 16 . So, these parameters would be of value to estimate the disease risk.…”

“…According to one post-mortem study, capillary dropout in the choriocapillaris of patients with diabetes is due to an increased number of polymorphonuclear leukocytes in the vascular lumen 23 . Heterogeneity of the choriocapillaris flow were similar to the changes which we reported in the fellow eyes of patients with unilateral age-related macular degeneration 16 , 17 , wherein low-grade chronic inflammation is known to be involved in the pathogenesis 24 , 25 . Diabetes is a chronic inflammatory disease 26 , and the heterogeneous progression of flow deficits may most likely reflect disease progression in response to systemic inflammatory conditions and not to focal stimuli.…”

Early Optical Coherence Tomography Biomarkers for Selected Retinal Diseases—A Review

“…The CCFA ratio was then compared between the two groups in four locations around the fovea. The mean CCFA ratio of the macular area was smaller in AMD high-risk fellow eyes with no particular findings such as drusen or MNV in the fundus than in the control eyes [10]. The decreased CCFA ratio observed in the AMD fellow eyes might indicate a decline in choriocapillaris flow, which could serve as an early indicator of AMD development in these eyes, according to the study.…”

Retinal Pigment Epithelial Abnormality and Choroidal Large Vascular Flow Imbalance Are Associated with Choriocapillaris Flow Deficits in Age-Related Macular Degeneration in Fellow Eyes

“…The CCFA ratio and the CV of the CCFA ratio, which represents the heterogeneity of the choriocapillaris deficits [ 13 ], were correlated with age in AMD fellow eyes and control eyes ( Figure 1 A,B); however, the mean CCFA ratio was significantly lower for AMD fellow eyes (58.1 ± 1.0%) than for control eyes (62.9 ± 1.4%, p = 0.031) ( Figure 1 C), and the mean CV of the CCFA ratio was greater in AMD fellow eyes (0.182 ± 0.007) ( Figure 1 D) than in control eyes (0.152 ± 0.0061, p = 0.002). This indicates that choriocapillaris flow deficits progress with age, and the findings were more severe in AMD fellow eyes, even in the absence of MNV or in the early stages of AMD.…”

Diabetic choriocapillaris flow deficits affect the outer retina and are related to hemoglobin A1c and systolic blood pressure levels

“…The cut-off values for choriocapillaris flow impairment in the current study were similar to our previous papers comparing eyes of control healthy patients and fellow eyes of unilateral age-related macular degeneration (AMD); the eyes with CCFA ratio < 60.0% and CV of the CCFA ratio ≥ 0.154 had an AMD risk 16 . So, these parameters would be of value to estimate the disease risk.…”

“…According to one post-mortem study, capillary dropout in the choriocapillaris of patients with diabetes is due to an increased number of polymorphonuclear leukocytes in the vascular lumen 23 . Heterogeneity of the choriocapillaris flow were similar to the changes which we reported in the fellow eyes of patients with unilateral age-related macular degeneration 16 , 17 , wherein low-grade chronic inflammation is known to be involved in the pathogenesis 24 , 25 . Diabetes is a chronic inflammatory disease 26 , and the heterogeneous progression of flow deficits may most likely reflect disease progression in response to systemic inflammatory conditions and not to focal stimuli.…”

Early Optical Coherence Tomography Biomarkers for Selected Retinal Diseases—A Review

“…The CCFA ratio was then compared between the two groups in four locations around the fovea. The mean CCFA ratio of the macular area was smaller in AMD high-risk fellow eyes with no particular findings such as drusen or MNV in the fundus than in the control eyes [10]. The decreased CCFA ratio observed in the AMD fellow eyes might indicate a decline in choriocapillaris flow, which could serve as an early indicator of AMD development in these eyes, according to the study.…”

Retinal Pigment Epithelial Abnormality and Choroidal Large Vascular Flow Imbalance Are Associated with Choriocapillaris Flow Deficits in Age-Related Macular Degeneration in Fellow Eyes

“…The CCFA ratio and the CV of the CCFA ratio, which represents the heterogeneity of the choriocapillaris deficits [ 13 ], were correlated with age in AMD fellow eyes and control eyes ( Figure 1 A,B); however, the mean CCFA ratio was significantly lower for AMD fellow eyes (58.1 ± 1.0%) than for control eyes (62.9 ± 1.4%, p = 0.031) ( Figure 1 C), and the mean CV of the CCFA ratio was greater in AMD fellow eyes (0.182 ± 0.007) ( Figure 1 D) than in control eyes (0.152 ± 0.0061, p = 0.002). This indicates that choriocapillaris flow deficits progress with age, and the findings were more severe in AMD fellow eyes, even in the absence of MNV or in the early stages of AMD.…”

Diabetic choriocapillaris flow deficits affect the outer retina and are related to hemoglobin A1c and systolic blood pressure levels

“…The cut-off values for choriocapillaris flow impairment in the current study were similar to our previous papers comparing eyes of control healthy patients and fellow eyes of unilateral age-related macular degeneration (AMD); the eyes with CCFA ratio < 60.0% and CV of the CCFA ratio ≥ 0.154 had an AMD risk 16 . So, these parameters would be of value to estimate the disease risk.…”

“…According to one post-mortem study, capillary dropout in the choriocapillaris of patients with diabetes is due to an increased number of polymorphonuclear leukocytes in the vascular lumen 23 . Heterogeneity of the choriocapillaris flow were similar to the changes which we reported in the fellow eyes of patients with unilateral age-related macular degeneration 16 , 17 , wherein low-grade chronic inflammation is known to be involved in the pathogenesis 24 , 25 . Diabetes is a chronic inflammatory disease 26 , and the heterogeneous progression of flow deficits may most likely reflect disease progression in response to systemic inflammatory conditions and not to focal stimuli.…”

Early Optical Coherence Tomography Biomarkers for Selected Retinal Diseases—A Review

“…The CCFA ratio was then compared between the two groups in four locations around the fovea. The mean CCFA ratio of the macular area was smaller in AMD high-risk fellow eyes with no particular findings such as drusen or MNV in the fundus than in the control eyes [10]. The decreased CCFA ratio observed in the AMD fellow eyes might indicate a decline in choriocapillaris flow, which could serve as an early indicator of AMD development in these eyes, according to the study.…”

Retinal Pigment Epithelial Abnormality and Choroidal Large Vascular Flow Imbalance Are Associated with Choriocapillaris Flow Deficits in Age-Related Macular Degeneration in Fellow Eyes

“…The CCFA ratio and the CV of the CCFA ratio, which represents the heterogeneity of the choriocapillaris deficits [ 13 ], were correlated with age in AMD fellow eyes and control eyes ( Figure 1 A,B); however, the mean CCFA ratio was significantly lower for AMD fellow eyes (58.1 ± 1.0%) than for control eyes (62.9 ± 1.4%, p = 0.031) ( Figure 1 C), and the mean CV of the CCFA ratio was greater in AMD fellow eyes (0.182 ± 0.007) ( Figure 1 D) than in control eyes (0.152 ± 0.0061, p = 0.002). This indicates that choriocapillaris flow deficits progress with age, and the findings were more severe in AMD fellow eyes, even in the absence of MNV or in the early stages of AMD.…”