Revealing the benefit of eye motion for acuity under emulated cone loss

Reviewer #1 (Public review):

The authors demonstrate an innovative approach to investigate the effect of cone dropout on visual acuity using their newly developed olo system. By systematically reducing the coverage of real-world input to the cone photoreceptor mosaic ("cone dropout condition"), the authors are able to assess how having fewer cones leads to reduced vision, in comparison to existing approaches ("pixel dropout condition").

The capture of a rich dataset, including cone imaging and eye motion, is valuable. Benchmarking with the prior literature, suggesting that good visual acuity can be maintained despite a 50% loss in cone density, is impressive. However, it is known that cone density varies dramatically from the peak cone density location in the foveal center to even a location a few degrees outside of the fovea. In addition, there is a high degree of subject-to-subject variation in peak cone density. Given that the C stimulus is hollow in the middle, the stimulus does not actually hit the location of the peak cone density but must land slightly outside of it. Therefore, considering the actual cone density of where the stimulus lands will be important to discuss and/or analyze.

The observation of visual acuity maintenance with cone dropout has been a longstanding mystery since the 2013/2018 papers by Ratnam and Foote. The authors should be commended for their approach to addressing this important question. However, there are some simplifications and assumptions being applied to make this jump (i.e., that a 50% reduction in cone stimulation in a healthy eye is comparable to a 50% reduction in cone density in a patient). It seems unlikely that, in a patient's eye, with cone dropout, there will be gaps in the mosaic. Not considering any other non-photoreceptor-related reasons for visual acuity loss, which can occur in patients, the cone aperture acceptance angle may be different due to changes in cone size or packing; the sensitivity of individual cones may also be reduced due to deficits in the visual cycle recovery, which could be affected in disease. Some of these limitations could be addressed and acknowledged more explicitly.

Overall, this is an impressive study incorporating state-of-the-art technology to probe the fundamental limits of human vision.