Ahmad, Noor-Us-Sabah1; Linton, Edward1; Wang, Jui-Kai1,2; Nellis, Julie1,2; Sohn, Elliot1; Kardon, Randy1,2
1University of Iowa Department of Ophthalmology and Visual Sciences; 2VA Center for the Prevention and Treatment of Visual Loss, Iowa City, IA
Purpose: Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly, and there are a paucity of treatment options for the non-exudative form in part because the pathogenesis is not fully understood. The hemodynamic theory of AMD suggests poor blood flow is a risk factor. Unlike OCT-A which provides a binary measure of flow, laser speckle flowgraphy (LSFG) gives quantitative information on blood flow velocity. In this retrospective case-control study, we analyzed LSFG-derived ocular blood flow indices of patients with dry AMD versus age-matched healthy controls.
Methods: Subjects with non-exudative AMD from the Iowa City VA Eye Clinic who had undergone LSFG scans were compared with age-matched controls. Blood flow quantified by MBR (mean blur rate) in arbitrary units (AU) was analyzed with the LSFG Analyzer software using binary threshold masking to separate it into chorioretinal flow (MT) and vascular flow (MV). A superpixel segmentation method was also used to quantify area of lowest choroidal blood flow (percentage area of MBR<5 AU). Student’s T-test was used to see difference in MT and area of lowest flow between groups. Multivariate logistic regression was used to assess the association between MT and AMD diagnosis controlling for age, sex, smoking status, diabetes, hypertension, hyperlipidemia diagnosis, BMI and ocular perfusion pressure as covariates. Mixed effects linear regression was used to evaluate predictors of blood flow.
Results: 24 eyes of 24 subjects with AMD and 21 eyes of 21 controls were included. Chorioretinal blood flow outside the major retinal vessels (MT) was lower in eyes with AMD compared with controls (5.3 ± 0.3 vs 7.9 ± 0.5, p< 0.0001 by t-test). Controlling for other subject and eye characteristics in the regression model, for every one-unit increase in MT, the odds ratio of AMD diagnosis was 0.36 in our population (95% CI 0.1-0.70, p=0.027). Intermediate and advanced AMD stage were significant predictors of lower blood flow after controlling for other covariates with mixed effects linear regression [intermediate: β -2.5±0.9, p=0.01; advanced: β -4.4±1.0, p=0.0003], and we found no relationship between blood flow and choroid vascularity index. Superpixel segmentation also showed a greater percentage of superpixels with lowest blood flow (MBR<5 AU) compared to controls (42 ± 5% vs 24 ± 5%, p=0.01 by t-test).
Conclusions: Eyes with AMD show a reduced ocular blood flow compared to controls that apparently exceeds the territory of retinal disease. Blood flow may serve as a potential target for AMD therapies in the future.
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