Progressive Choriocapillaris Changes on Optical Coherence Tomography Angiography Correlate With Stage Progression in AMD

Abstract

Purpose: We investigated the association between inner choroid flow deficit percentage (IC-FD%) using swept-source optical coherence tomography angiography (SS-OCTA) and progression of AMD.

Methods: Retrospective, observational study including 64 eyes (42 participants) with early or intermediate AMD at baseline. Participants had two or more consecutive swept-source optical coherence tomography angiography covering a period of at least 18 months. Demographics, visual acuity, and AMD staging based on Beckman classification were reviewed. OCT was analyzed for hyperreflective foci, subretinal drusenoid deposits, hyporeflective drusen cores, and subfoveal choroidal thickness. IC-FD% was measured within the central 3- and 6-mm using a 16-µm slab, after compensation and binarization (Phansalkar method). Mixed-effects Cox regression models assessed the association between imaging biomarkers and AMD progression.

Results: During follow-up (37 ± 9 months), 4 eyes with early AMD (31%) progressed to intermediate AMD and 30 (59%) eyes with intermediate AMD developed late AMD (19 geographic atrophy; 11 wet AMD). Baseline hyporeflective drusen core was associated with geographic atrophy development (P < 0.01), whereas greater IC-FD% (3-mm) was associated with wet AMD (P = 0.03). Time-varying analysis showed that faster subfoveal choroidal thickness reduction and IC-FD% (6-mm) increase were associated with geographic atrophy onset (P < 0.05), whereas IC-FD% (3-mm) increase was associated with wet AMD (P = 0.03). Notably, greater IC-FD% increases in the 3 mm (area under the curve = 0.72) and 6 mm (area under the curve = 0.89) were better predictive of wet AMD and geographic atrophy development, respectively.

Conclusions: Our longitudinal IC-FD% assessment emphasizes the role of progressive choriocapillaris changes as a biomarker for AMD progression. Our findings support that widespread choriocapillaris alterations (6 mm) may precede progression to geographic atrophy, whereas more central choriocapillaris loss (3 mm) may provide an ischemic stimulus for wet AMD.

Figure 1.

Schematic representation of the inner choroid flow deficit percentage (IC-FD%) analysis. A customized angiography choriocapillaris slab (offset, 4–20 µm) placed underneath the Bruch's membrane and the corresponding inverted structural en face slab were multiplied to obtain a compensated image. The resulting image was binarized using a low-contrast local thresholding technique (Phansalkar method; radius = 4 and 15 pixels). Two masks were generated from the superficial capillary plexus and the drusen map to highlight the structures that might exert a shadowing effect on the underlying choriocapillaris. The IC-FD% was then measured in the central 3- and 6-mm regions using the ‘Analyze Particle’ tool after excluding the areas detected on vessel and drusen masks.

Figure 2.

Kaplan-Meier estimates for the incidence of AMD stage progression and visual acuity (VA) loss during the follow-up. Incidence rates for any AMD progression (green lines), geographic atrophy development (red lines), and wet AMD conversion (blue lines) were estimated to be 33.5, 20.4, and 11.4, person-years, respectively. The estimated incidence rate for VA loss of at least three Early Treatment for Diabetic Retinopathy Study (ETDRS) lines was of 13.9 person-years; this characteristic was particularly evident in eyes converting to wet AMD.

Figure 3.

Mixed-effect Cox regression models to estimate AMD progression from baseline (top) and time-dependent (bottom) imaging characteristics. The occurrence of any AMD progression was associated with the presence of hDC (HR, 4.43; P = 0.004), subretinal drusenoid deposits (SDDs; HR, 2.83; P = 0.04), and greater IC-FD% in the central 3 mm (HR, 1.26; P = 0.007) at baseline and with faster increase of IC-FD% in the central 3-mm circles (HR, 1.56; P = 0.02) and 6-mm circles (HR, 2.02; P = 0.01) over the follow-up. Progression to geographic atrophy was associated with the presence of hDC at baseline (HR, 8.94; P = 0.004) and with faster subfoveal choroidal thinning (HR, 1.25; P = 0.04) and IC-FD% increase in the 6-mm circle (HR, 3.32; P = 0.01). Conversion to wet AMD was associated with greater IC-FD% in the 3-mm circle at baseline (HR, 1.36; P = 0.03) and faster increase during the follow-up (HR, 1.87; P = 0.03).

Figure 4.

Expected values and 95% confidence intervals for IC-FD% in our AMD cohort over the follow-up. (Top) Eyes progressing to more advanced AMD stages exhibited a faster increase in IC-FD% both in the central 3- and 6-mm circles (red line), reaching a plateau after approximately 24 months of follow-up. (Bottom) When assessing intermediate AMD, both eyes progressing to geographic atrophy (red line) and those converting to wet AMD (blue line) showed a greater increase in IC-FD% in the two analyzed circles.