In this current study, a new analysis technique was applied to ICG angiography to more objectively evaluate choroidal perfusion in subjects with non-neovascular AMD compared with subjects with normal eyes. These techniques have been previously described.15
In brief, the entire 40 degree ICG angiogram is divided into a number of small regions (Fig 2) and dilution curves (Fig 3) are created for each region. Although the exact concentration of ICG in each region cannot be determined, simultaneous acquisition of dye dilution curves from these regions within the choroid facilitates comparison of relative concentrations between these regions and allows for assessment of the various timing parameters. Since the six analysis regions are identically positioned on each subject's angiogram, the resulting analysis represents an objective evaluation of choroidal perfusion characteristics and does not rely on subjective assessment. In addition, ICG facilitates study of the choroidal circulation for several reasons. Firstly, ICG better delineates the choroidal circulation than fluorescein because the near infrared light absorbed by ICG penetrates the retina pigment epithelium better than the shorter wavelength absorbed by fluorescein. Also, unlike fluorescein, ICG is strongly bound to plasma proteins, which prevents diffusion of the compound through the fenestrated choroidal capillaries, and permits better delineation of choroidal details. The use of scanning laser ophthalmoscopy for ICG angiography further improves the technique as the confocal design eliminates scattered and reflected light, while the single spot laser illumination improves contrast.
In the current study, subjects with non-neovascular AMD showed significant delay and heterogeneity of filling within the perifoveal region of non-neovascular AMD patients when compared with normal age matched controls. As noted above, the haemodynamic heterogeneity is measured within each eye and not between subjects; consequently, this statistically significant result does not originate from differences in AMD manifestations between subjects, but from increased haemodynamic heterogeneity between the analysed regions of the choroid in an AMD subject compared with a control subject. These differences were most pronounced in the perifoveal regions, suggesting that the choroidal perfusion anomalies in non-neovascular AMD show some preferential involvement of the perifoveal choroid. The pathophysiological basis for this perifoveal change is unclear; it is intriguing that the other changes observed in AMD (drusen, RPE mottling, choroidal neovascularisation, etc) also preferentially present in the macula instead of extramacularly. Although the subjects in this study were not sex matched, sex differences between the groups are unlikely to account for the results, because there was no difference between sex groups when the results of the area dilution analysis were compared between sexes within each of the AMD and control groups. Likewise, it is unlikely that the differences in systolic blood pressures between the groups account for the results since there was no significant difference in ocular perfusion pressure between the groups. Compared to blood pressure, ocular perfusion pressure (2/3 mean arterial pressure − IOP) is believed to more accurate reflect the vascular inflow to the eye since it accounts for the intraocular pressure; consequently this parameter is commonly used for assessing ocular perfusion in ocular blood flow studies.16–18
Furthermore, these results were not unexpected and very consistent with previous studies, which have suggested very similar choroidal perfusion abnormalities in AMD using conventional angiographic techniques.
In particular, this study corroborates and amplifies results from previous studies using fluorescein angiography,1–6
laser Doppler flowmetry,7
colour Doppler imaging,8,9
and ICG angiography,12
For example, delayed choroidal filling has been noted angiographically in patients with neovascular AMD.1–3
The use of fluorescein angiography to study the choroidal circulation has several limitations that include leakage of fluorescein from the choroidal circulation, and the overlying retinal circulation that complicates analysis. Nevertheless, the results obtained in the current study are consistent with these previous fluorescein angiographic studies. One group recently used laser Doppler flowmetry in subjects with non-neovascular AMD to show that the choroidal blood flow was decreased at the centre of the fovea compared to a control group.7
This technique cannot be readily applied outside the foveal centre as the overlying retinal circulation would Doppler shift the reflected light from the laser and prevent analysis of the choroid. This study and the current study, however, are complementary; this earlier study showed alterations in choroidal flow in the foveal centre and current study confirmed alterations with some perifoveal region specificity, although the foveal centre itself was not measured. Colour Doppler imaging has been used to evaluate the retrobulbar vasculature in AMD; two groups have found statistically significant differences in the central retinal and posterior ciliary arteries in patients with AMD compared to controls.8,9
This technique, however, assays the retrobulbar vessels and consequently better correlates with bulk flow to the choroid (posterior ciliary arteries) and to the retina (central retinal artery) without any macular region specificity. Bischoff and Flower were first to demonstrate that the ICG angiograms of AMD cases were abnormal,10
and Prunte and Niesel were first to subject ICG angiograms from AMD patients to quantitative analysis, using parameters such as the mean time for arterial, capillary and venous filling and a parameter corresponding to the amount of perfused capillaries in the choroid.11
Another group more recently used a new analysis technique based on indocyanine green angiography to compare the choroidal circulation in patients with AMD to a control group, and noted a statistically significant increased frequency of presumed macular watershed filling, which they described as “characteristic vertical, angled, or stellate-shaped zones of early-phase indocyanine green videoangiographic hypofluorescence, assumed to be hypoperfusion, which disappeared in the early phase of the angiogram.”12
This technique, however, requires subjective interpretation and cannot provide quantitative analysis of choroidal filling parameters. In addition, this study included a heterogeneous population of both neovascular and non-neovascular AMD patients.
In summary, the current study objectively demonstrates delayed and heterogeneous filling of the choroid in patients with non-neovascular AMD with some perifoveal region specificity. These results corroborate and amplify the work of previous authors as detailed above. Future studies using this technique should be designed to fully compare perfusion characteristics in subjects with bilateral non-neovascular AMD to subjects with unilateral neovascular AMD in the fellow eye. Assessing perfusion differences between these bilateral non-neovascular and unilateral neovascular forms would be of interest in the future since the underlying pathophysiology may differ between these populations. For example, it is unclear if the choroidal perfusion defects demonstrated in non-neovascular AMD lead to localised choroidal ischaemia and a subsequent neovascular response. Finally, it should be noted that it is not possible to determine if the choroidal perfusion abnormalities has a causative role in non-neovascular AMD, if they are simply an association with, or result of, another primary alteration. Much further study is warranted, given the prevalence of AMD, the limited understanding of its pathophysiology, the devastating consequences, and the lack of effective treatment.