Abstract
Purpose :
Cone outer segment (COS) length is a common biomarker for disease severity in retinal degenerations such as retinitis pigmentosa (RP). The optoretinogram (ORG) has emerged as a metric for cone function and dysfunction. Here we test the hypothesis that retinal dysfunction as assessed by ORG is correlated with COS length in RP.
Methods :
ORGs were acquired from 4 RP subjects (age 25-29) and 3 age-matched controls using line-field spectral domain adaptive optics-optical coherence tomography (AO-OCT). Regions of interest (ROIs) ranged between 1° and 3° retinal eccentricity and spanned the normal-appearing and disease transition zone (TZ) states. The change in optical path length (ΔOPL) between the COS tips and inner-outer segment junction (ISOS) reflections in AO-OCT was calculated following a 44% LM-cone bleach with 528 nm light stimulus. COS length was evaluated by identifying the ISOS & COST at sub-pixel resolution using a 3D center-of-mass algorithm in 5138 control and 3323 RP cones. Cones were clustered as either high or low ΔOPL for 2-way ANOVA and linear regression comparisons.
Results :
Control COS lengths were 41.95±3.82μm, 36.10±3.46μm, and 32.59±3.25μm for 1°, 2° and 3° eccentricity. On average across eccentricity, low ΔOPL cones had 11.2±3.6% shorter COS lengths than high ΔOPL cones in controls. While the range of RP COS lengths overlapped with controls, they were significantly more variable (n=8/8 ROIs, p<0.05) and shorter (n=6/8 ROIs, p<0.0005). However, in one normal appearing ROI in RP at 1° eccentricity, COS length was significantly longer than controls (p<0.0005). A slight but significant correlation was found between COS length and ΔOPL in the high ΔOPL group in controls and in 3 out of 4 normal-appearing RP ROIs (R2 = 0.02-0.15, p<0.05), but not in the TZ of RP where ΔOPL was reduced (n=4/4, p>0.05). Overall, COS length alone accounts for only a minuscule fraction of the variability observed in ΔOPL.
Conclusions :
COS lengths and ΔOPL are more variable in RP subjects, and single cone measures of both parameters are sensitive to dysfunction and heterogeneity that is undetectable by conventional methods. The larger variability in ΔOPL in RP is unexplained by COS length but could be accounted for by abnormal waveguiding leading to inter-cone variability in photoisomerization or abnormalities in the phototransduction cascade.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.