Examining the concordance of retinal ganglion cell counts generated using measures of structure and function

There are several indirect methods used to estimate retinal ganglion cell (RGC) count in an individual eye, but there is limited information as to the agreement between these methods. In this work, RGC receptive field (RGC-RF) count underlying a spot stimulus (0.43°, Goldmann III) was calculated and compared using three different methods.

RGC-RF count was calculated at a retinal eccentricity of 2.32 mm for 44 healthy adult participants (aged 18-58 years, refractive error -9.75 DS to +1.75 DS) using: (i) functional measures of achromatic peripheral grating resolution acuity (PGRA), (ii) structural measures of RGC-layer thickness (OCT-model, based on the method outlined by Raza and Hood) and (iii) scaling published histology density data to simulate a global expansion in myopia (Histology-Balloon).

Whilst average RGC-RF counts from the OCT-model (median 105.3, IQR 99.6-111.0) and the Histology-Balloon model (median 107.5, IQR 97.7-114.6) were similar, PGRA estimates were approximately 65% lower (median 37.7, IQR 33.8-46.0). However, there was poor agreement between all three methods (Bland-Altman 95% limits of agreement; PGRA/OCT: 55.4; PGRA/Histology-Balloon 59.3; OCT/Histology-Balloon: 52.4). High intersubject variability in RGC-RF count was evident using all three methods.

The lower PGRA RGC-RF counts may be the result of targeting only a specific subset of functional RGCs, as opposed to the coarser approach of the OCT-model and Histology-Balloon, which include all RGCs, and also likely displaced amacrine cells. In the absence of a 'ground truth', direct measure of RGC-RF count, it is not possible to determine which method is most accurate, and each has limitations. However, what is clear is the poor agreement found between the methods prevents direct comparison of RGC-RF counts between studies utilising different methodologies and highlights the need to utilise the same method in longitudinal work.