Our findings also have implications in the clinical use of OCTA to evaluate the RPCP in glaucoma and other optic neuropathies. In areas where the RPCP-CD is near the ceiling value (saturated) due to the overlap of multiple capillary layers, minor loss of capillaries may not be easily detected. Thus, the immediate peripapillary area is actually not the best location to image the RPCP for optimal detection of early glaucoma. The investigation of peripapillary retina perfusion by OCTA in glaucoma started with the use of a 3-mm
2 scan area centered on the disc.
14 Within such a small area, nearly all RPCP is near saturation density (
Fig. 7). Current commercial OCTA systems use larger scan areas of 4.5 or 6.0 mm, which should improve the detection sensitivity for early glaucoma. Our results indicate that the smallest efficient rectangular scan pattern that would cover the entire dense (CD > half maximum) RPCP-CD area would need to be 8-mm vertical × 7-mm horizontal square and be temporally displaced by 1.0 mm and inferiorly displaced by 0.5 mm (
Fig. 7). Wider scans beyond this limit would have diminishing return, but the size of commercial OCTA is not close to this limit yet. The importance of a wider RPCP measurement has been demonstrated in clinical studies. Using a 4.5-mm
2 (OCTA) scan area, Yarmohamadi et al.
29 found that the diagnostic accuracy for perimetric glaucoma was highest for the whole-image retinal VD (not excluding large vessels), which had an area under the receiver operating curve (AROC) of 0.94. In comparison, the diagnostic accuracy of the peripapillary retinal vessel density in a 0.75-mm-wide annulus (∼3-mm outer diameter) around the disc was significantly worse (AROC = 0.83). Using a 4.5-mm
2 scan area and 4.0-mm
2 analytic area and focusing on the RPCP instead of all-plexus retinal VD, we have results in 40 mostly mild perimetric glaucoma subjects and 38 normal subject that yielded an AROC of 0.941 (Edmunds B, et al.
IOVS 2017;58:ARVO E-Abstract 721). Theoretically, RPCP-CD could detect glaucoma damage at an early stage when ganglion cells and nerve fibers are dysfunctional, less metabolically active, and require less perfusion. This would occur prior to cell death, axon loss, and NFL thinning. Case series have shown that RPCP changes precede NFL thinning in glaucoma patients with focal lamina cribrosa defects.
30 Good diagnostic accuracy is already possible using 4.5-mm
2 scans. The current study suggests that further improvement may be possible using an even larger scan area. Although the use of adaptive-optics OCTA could also reduce RPCP-CD saturation, it is probably a more difficult technical solution than simply scanning and analyzing a wider area with high-speed OCTA.