Hypofluorescent ICGA spots: prevalence, characteristics and associated features in Age-related Macular degeneration

Purpose To evaluate the frequency of detecting age-related scattered hypofluorescent spots (ASHS) on indocyanine green angiography in the fellow eyes of patients presenting with unilateral neovascular age-related macular degeneration. Additionally, we compare systemic and ocular features between the ASHS group with eyes with homogenous ICGA and eyes with visible drusen. Methods Patients with unilateral neovascular AMD underwent protocolized examination including a best-corrected visual acuity, slit-lamp biomicroscopy, OCT, indocyanine green angiography (ICGA) and swept-source OCTA. ICGA images were used to evaluate the presence of scattered hypofluorescent spots. Choriocapillaris vessel density was determined using OCTA. Serum lipid profile and medical history were evaluated. Development of incident exudative AMD over 12-months was recorded. Results We included 142 eyes/ patients (mean age 70.8 (8.2) years, 70.4% male). The subtype of MNV in the fellow eye was PCV (60.5%), type 1 or mixed type (26.1%), pure type 2 MNV (9.9%), and type 3 MNV (3.5%). Three groups were identified according to ICGA appearance: Homogenous (n=48, 33.8%), ASHS (n=46, 32.3%) and Drusen/RPD group (n=48, 33.8%). The ASHS group had similar age, gender, ethnicity and medical history as patients in the Homogenous group, but was significantly younger than the Drusen/RPD group (68.4 ± 7.3 vs 75.5 ± 8.4 years, p<0.001). Regarding ocular features, the ASHS group had shorter axial length (23.52 ± 1.28 vs 24.32 ± 1.49, p=0.047) than the homogenous group, and had better BCVA (0.17 ± 0.13 vs 0.29 ± 0.24 logMAR, p=0.012) and greater subfoveal choroidal thickness (262.28 ± 98.64 vs 183.04 ± 80.88 μm, p=0.006) than the drusen/RPD group . Choriocapillaris vessel density was similar between the ASHS group and homogenous gropu (71.1 ± 2.9% vs 71.2 ± 4.3% p=0.934), while the drusen/RPD group had significantly lower CC vessel density (64.6 ± 6.8%, p=0.002). The subtype of neovascularization in the fellow eye was predominantly PCV in the ASHS and homogenous groups (78.26% and 75.00% and, p=0.78) but was significantly lower in the drusen/RPD group (29.2%, p<0.001). The ASHS group had significantly lower total cholesterol (4.31 ± 1.10) compared to the homogenous group (4.56 ± 1.48 mmol/L, p=0.039) and the drusen/RPD group (4.84 ± 1.60 mmol/L, p=0.028) after adjusting for lipid-lowering medication use. Conclusions One in three fellow eyes of patients with unilateral nAMD in this Asian population exhibited ASHS lesions. CC vessel density based on OCTA was similar between the ASHS group and the homogenous group, further supporting the hypothesis for reduced transit of ICG-laden lipoproteins across the Bruch's membrane.