Optically Isolating Photoreceptors as AMD Biomarkers using Directional OCT

Abstract

 

Purpose

 

To use Directional Optical Coherence Tomography (D-OCT) to harness the directional reflectivity properties of photoreceptors in eyes with Age-related Macular Degeneration (AMD).

 

Methods

 

D-OCT of the Outer Retina in AMD (DOCTORA) is an ongoing IRB-approved one-year natural history study of 48 subjects with drusen and geographic atrophy (GA) and 25 control subjects. A D-OCT acquisition protocol using Cirrus HD-OCT with multiple image sets obtained through multiple pupil entry positions was performed at baseline and every three months. Custom MATLAB analysis was then used to delineate and measure the outer nuclear layer (ONL) and Henle fiber layer (HFL) thicknesses from cross-sectional image sets and volumes from multiple macular cube sets. Custom registration, normalization, and display software was used to visualize reflectivity changes in composite D-OCT images. Visual acuity, fundus photography and autofluorescence measures were compared with D-OCT findings.

 

Results

 

D-OCT image sets were successfully acquired by multiple OCT operators using a standardized protocol. 65% (92/142) of baseline cross-sectional D-OCT sets could be successfully registered and analyzed for directional optical effects using a fully automated approach. 95% (132/142) had at least two cross-sectional scans that could be registered using a semi-automated approach. Unambiguous differentiation of ONL and HFL was possible in all registered scans. Increased visualization of the ONL/HFL boundary in the quadrant contrateral to the pupil entry position occurred in each macular cube, which could be integrated to provide average ONL and HFL measurements within the central 5 mm of the macula. Baseline mean (SD) ONL volume (mm³) for control eyes was 2.24 (0.18), for drusen eyes was 2.26 (0.18) and for GA eyes was 2.13 (0.29), and were 71%, 72% and 74%, respectively, of what would be measured had HFL been included. Compared to controls, the directional optical effects exhibited by the hyper-reflective photoreceptor bands was altered overlying drusen and near the edges of GA, indicating an abnormal orientation or disruption.

 

Conclusions

 

D-OCT provides independent cross-sectional and volumetric measurements of ONL and HFL. Visualization of photoreceptor orientation is also permitted, which may be an indicator of photoreceptor integrity. Analysis of these novel metrics in the DOCTORA study may reveal early imaging biomarkers of AMD progression.