OCT angiography indices and the choroidal vascularity index in wild-type transthyretin (TTR) amyloidosis (ATTRwt)

**Background:** Transthyretin amyloidosis (ATTR) includes wild-type (ATTRwt) and hereditary (ATTRv) forms. Ocular involvement in ATTRv is well-documented, but retinal and choroidal changes in ATTRwt are poorly understood. This study aimed to evaluate vessel density (VD) indices and the choroidal vascularity index (CVI) as potential biomarkers for retinal and choroidal vascular involvement in ATTRwt patients.

**Methods:** This retrospective observational case-control study included 18 patients with confirmed ATTRwt (Group 1) and 16 age-matched healthy controls (Group 2). All participants underwent swept-source OCT (SS-OCT) and OCT angiography (OCTA). Exclusion criteria included diabetes, atherosclerotic vasculopathy, glaucoma, macular or retinal disorders, and media opacities. VD was measured in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) across five ETDRS sectors (central, superior, inferior, nasal, temporal). CVI was calculated using ImageJ software by binarizing choroidal images to determine total choroidal area (TCA), luminal area (LA), and stromal area (SA). Central foveal thickness (CFT) and choroidal thickness (CT) were also measured. Statistical analysis used Student's t-test and Brunner-Munzel test.

**Key Results:** The mean VD was significantly reduced in ATTRwt patients compared to controls in all three plexuses across all ETDRS sectors (p < 0.0001 for most comparisons). For example, central SCP VD was 15.66 ± 3.59% in ATTRwt vs. 19.41 ± 1.61% in controls (p < 0.0001); central DCP VD was 23.45 ± 4.72% vs. 28.45 ± 2.68% (p = 0.0007); central CC VD was 25.67 ± 4.33% vs. 45.71 ± 5.08% (p = 0.0005). The median CVI was lower in ATTRwt (32.86, range 21.36–70.22) vs. controls (41.57, range 22.90–62.95), but this difference was not statistically significant (p = 0.08). However, TCA (p = 0.002), LA (p = 0.003), and SA (p = 0.009) were significantly reduced in ATTRwt. Choroidal thickness showed a trend toward reduction in ATTRwt (p = 0.08), while CFT did not differ significantly. Subgroup analysis within ATTRwt patients (12 on tafamidis therapy vs. 6 untreated) showed no significant differences in VD or CVI. Anterior segment findings included conjunctival ectasia (55.5%), corneal deposition (33.3%), lens deposition (22.2%), and vitreous opacities (66.6%); no scalloped pupils or retinal deposits were observed.

**Clinical Implications:** These findings indicate that ATTRwt patients have subclinical retinal and choroidal microvascular impairment detectable by OCTA and CVI, even without visual decline. The reduced VD and CVI suggest that both retinal and choroidal circulations are compromised, potentially due to amyloid deposition. These non-invasive imaging biomarkers could aid in early diagnosis, monitoring disease progression, and assessing treatment response (e.g., tafamidis). The lack of correlation with visual acuity suggests these changes precede functional loss, highlighting their value for early detection. Limitations include small sample size, lack of axial length measurement, and short follow-up. Future longitudinal studies are needed to track changes over time and correlate with systemic parameters.